Breast Cancer

Key clinical point: Patients with microinvasive breast cancer (BC) had a significantly higher risk for local recurrence and comparable rates of distant recurrence and death compared with patients with T1a-2 BC.

Major finding: Although the 10-year local recurrence rate was significantly higher in patients with microinvasive vs T1a-2 BC (hazard ratio 3.73; P < .001), the 10-year distant recurrence risk (P = .36) and overall survival rates (P = .14) were similar between both patient populations.

Study details: Findings are from the Canadian Hypofractionation trial including 1234 patients with T1-2 N0 invasive BC who were randomly assigned to receive hypofractionated or conventional fractionated whole breast irradiation, of which 3% of patients had microinvasive BC.

Disclosures: Dr Whelan declared receiving support from the Canada Research Chair in Breast Cancer Research and research funding unrelated to this study.

Source: Goldberg M et al. Long-term outcomes and effects of hypofractionated radiotherapy in microinvasive breast cancer: Analysis from a randomized trial. Breast. 2023;68:189-193 (Feb 9). Doi: 10.1016/j.breast.2023.02.005

Key clinical point: Patients with microinvasive breast cancer (BC) had a significantly higher risk for local recurrence and comparable rates of distant recurrence and death compared with patients with T1a-2 BC.

Major finding: Although the 10-year local recurrence rate was significantly higher in patients with microinvasive vs T1a-2 BC (hazard ratio 3.73; P < .001), the 10-year distant recurrence risk (P = .36) and overall survival rates (P = .14) were similar between both patient populations.

Study details: Findings are from the Canadian Hypofractionation trial including 1234 patients with T1-2 N0 invasive BC who were randomly assigned to receive hypofractionated or conventional fractionated whole breast irradiation, of which 3% of patients had microinvasive BC.

Disclosures: Dr Whelan declared receiving support from the Canada Research Chair in Breast Cancer Research and research funding unrelated to this study.

Source: Goldberg M et al. Long-term outcomes and effects of hypofractionated radiotherapy in microinvasive breast cancer: Analysis from a randomized trial. Breast. 2023;68:189-193 (Feb 9). Doi: 10.1016/j.breast.2023.02.005

Key clinical point: Patients with microinvasive breast cancer (BC) had a significantly higher risk for local recurrence and comparable rates of distant recurrence and death compared with patients with T1a-2 BC.

Major finding: Although the 10-year local recurrence rate was significantly higher in patients with microinvasive vs T1a-2 BC (hazard ratio 3.73; P < .001), the 10-year distant recurrence risk (P = .36) and overall survival rates (P = .14) were similar between both patient populations.

Study details: Findings are from the Canadian Hypofractionation trial including 1234 patients with T1-2 N0 invasive BC who were randomly assigned to receive hypofractionated or conventional fractionated whole breast irradiation, of which 3% of patients had microinvasive BC.

Disclosures: Dr Whelan declared receiving support from the Canada Research Chair in Breast Cancer Research and research funding unrelated to this study.

Source: Goldberg M et al. Long-term outcomes and effects of hypofractionated radiotherapy in microinvasive breast cancer: Analysis from a randomized trial. Breast. 2023;68:189-193 (Feb 9). Doi: 10.1016/j.breast.2023.02.005

Key clinical point: Programmed cell death-1 ligand-2 (PD-L2) protein levels were high in approximately one-third of estrogen receptor-positive (ER+) breast cancer (BC) tumors and were associated with greater odds of disease recurrence.

Major finding: High levels of PD-L2 protein were present in 33% of ER+ tumors and were associated with shorter progression-free survival in the entire cohort of patients with ER+ BC (hazard ratio [HR] 2.0; P < .001) and in the subgroup of patients treated with adjuvant chemotherapy (HR 3.4; P < .001).

Study details: Findings are from a retrospective study including patients with ER+ BC who were categorized into the main study cohort (n = 684) and the external validation cohort (n = 273).

Disclosures: This study was supported by grants from Susan G. Komen, US National Institutes of Health, and other sources. The authors declared serving in leadership, employment, or consulting or advisory roles or receiving funding, honoraria, or travel and accommodation expenses from several sources.

Source: Chervoneva I et al. High PD-L2 predicts early recurrence of ER-positive breast cancer. JCO Precis Oncol. 2023;7:e2100498 (Jan 18). Doi: 10.1200/PO.21.00498

Key clinical point: Programmed cell death-1 ligand-2 (PD-L2) protein levels were high in approximately one-third of estrogen receptor-positive (ER+) breast cancer (BC) tumors and were associated with greater odds of disease recurrence.

Major finding: High levels of PD-L2 protein were present in 33% of ER+ tumors and were associated with shorter progression-free survival in the entire cohort of patients with ER+ BC (hazard ratio [HR] 2.0; P < .001) and in the subgroup of patients treated with adjuvant chemotherapy (HR 3.4; P < .001).

Study details: Findings are from a retrospective study including patients with ER+ BC who were categorized into the main study cohort (n = 684) and the external validation cohort (n = 273).

Disclosures: This study was supported by grants from Susan G. Komen, US National Institutes of Health, and other sources. The authors declared serving in leadership, employment, or consulting or advisory roles or receiving funding, honoraria, or travel and accommodation expenses from several sources.

Source: Chervoneva I et al. High PD-L2 predicts early recurrence of ER-positive breast cancer. JCO Precis Oncol. 2023;7:e2100498 (Jan 18). Doi: 10.1200/PO.21.00498

Key clinical point: Programmed cell death-1 ligand-2 (PD-L2) protein levels were high in approximately one-third of estrogen receptor-positive (ER+) breast cancer (BC) tumors and were associated with greater odds of disease recurrence.

Major finding: High levels of PD-L2 protein were present in 33% of ER+ tumors and were associated with shorter progression-free survival in the entire cohort of patients with ER+ BC (hazard ratio [HR] 2.0; P < .001) and in the subgroup of patients treated with adjuvant chemotherapy (HR 3.4; P < .001).

Study details: Findings are from a retrospective study including patients with ER+ BC who were categorized into the main study cohort (n = 684) and the external validation cohort (n = 273).

Disclosures: This study was supported by grants from Susan G. Komen, US National Institutes of Health, and other sources. The authors declared serving in leadership, employment, or consulting or advisory roles or receiving funding, honoraria, or travel and accommodation expenses from several sources.

Source: Chervoneva I et al. High PD-L2 predicts early recurrence of ER-positive breast cancer. JCO Precis Oncol. 2023;7:e2100498 (Jan 18). Doi: 10.1200/PO.21.00498

Key clinical point: The addition of abemaciclib to endocrine therapy (ET) demonstrated robust treatment benefits regardless of menopausal status in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−), high-risk early breast cancer (BC).

Major finding: Abemaciclib+ET significantly improved invasive disease-free survival (iDFS; hazard ratio 0.785; nominal P = .0268) in postmenopausal women with HR+/HER2− BC and led to even greater iDFS improvement (hazard ratio 0.578; P < .0001) in premenopausal women. No new safety events were reported.

Study details: Findings are from an exploratory analysis of the monarchE trial including 5637 patients with HR+/HER2−, node-positive, high-risk early BC who were randomly assigned to receive standard of care ET with/without adjuvant abemaciclib, of which 43.5% and 56.4% of patients were premenopausal and postmenopausal, respectively.

Disclosures: This study was funded by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly. The other authors reported ties with several sources, including Eli Lilly.

Source: Paluch-Shimon S et al, on behalf of the monarchE investigators. Efficacy and safety results by menopausal status in monarchE: adjuvant abemaciclib combined with endocrine therapy in patients with HR+, HER2−, node-positive, high-risk early breast cancer. Ther Adv Med Oncol. 2023 (Feb 3). Doi: 10.1177/17588359231151840

Key clinical point: The addition of abemaciclib to endocrine therapy (ET) demonstrated robust treatment benefits regardless of menopausal status in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−), high-risk early breast cancer (BC).

Major finding: Abemaciclib+ET significantly improved invasive disease-free survival (iDFS; hazard ratio 0.785; nominal P = .0268) in postmenopausal women with HR+/HER2− BC and led to even greater iDFS improvement (hazard ratio 0.578; P < .0001) in premenopausal women. No new safety events were reported.

Study details: Findings are from an exploratory analysis of the monarchE trial including 5637 patients with HR+/HER2−, node-positive, high-risk early BC who were randomly assigned to receive standard of care ET with/without adjuvant abemaciclib, of which 43.5% and 56.4% of patients were premenopausal and postmenopausal, respectively.

Disclosures: This study was funded by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly. The other authors reported ties with several sources, including Eli Lilly.

Source: Paluch-Shimon S et al, on behalf of the monarchE investigators. Efficacy and safety results by menopausal status in monarchE: adjuvant abemaciclib combined with endocrine therapy in patients with HR+, HER2−, node-positive, high-risk early breast cancer. Ther Adv Med Oncol. 2023 (Feb 3). Doi: 10.1177/17588359231151840

Key clinical point: The addition of abemaciclib to endocrine therapy (ET) demonstrated robust treatment benefits regardless of menopausal status in women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−), high-risk early breast cancer (BC).

Major finding: Abemaciclib+ET significantly improved invasive disease-free survival (iDFS; hazard ratio 0.785; nominal P = .0268) in postmenopausal women with HR+/HER2− BC and led to even greater iDFS improvement (hazard ratio 0.578; P < .0001) in premenopausal women. No new safety events were reported.

Study details: Findings are from an exploratory analysis of the monarchE trial including 5637 patients with HR+/HER2−, node-positive, high-risk early BC who were randomly assigned to receive standard of care ET with/without adjuvant abemaciclib, of which 43.5% and 56.4% of patients were premenopausal and postmenopausal, respectively.

Disclosures: This study was funded by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly. The other authors reported ties with several sources, including Eli Lilly.

Source: Paluch-Shimon S et al, on behalf of the monarchE investigators. Efficacy and safety results by menopausal status in monarchE: adjuvant abemaciclib combined with endocrine therapy in patients with HR+, HER2−, node-positive, high-risk early breast cancer. Ther Adv Med Oncol. 2023 (Feb 3). Doi: 10.1177/17588359231151840

Key clinical point: In patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC), adding endocrine therapy (ET) to dual anti-HER2 targeted therapy after chemotherapy improved progression-free survival (PFS) without increasing the rate of adverse events.

Major finding: There was a significant improvement in 5-year PFS with vs without the addition of ET (hazard ratio 0.59; P = .031). Nausea and vomiting were more common in patients who did not vs did receive ET (21% vs 7%; P = .010).

Study details: This study analyzed the real-world data of 147 patients with HER2+/HR+ metastatic BC from a prospective registry who received first-line chemotherapy plus trastuzumab and pertuzumab with (n = 91) or without (n = 56) concurrent ET.

Disclosures: This study did not receive any funding. Some authors declared serving on the advisory board for or receiving research funding, speaker honoraria, or travel grants from several sources.

Source: Loft M et al. Addition of endocrine therapy to dual anti-HER2 targeted therapy in initial treatment of HER2 + /HR + metastatic breast cancer. Breast Cancer Res Treat. 2023;198:67-74 (Jan 9). Doi: 10.1007/s10549-022-06856-1

Key clinical point: In patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC), adding endocrine therapy (ET) to dual anti-HER2 targeted therapy after chemotherapy improved progression-free survival (PFS) without increasing the rate of adverse events.

Major finding: There was a significant improvement in 5-year PFS with vs without the addition of ET (hazard ratio 0.59; P = .031). Nausea and vomiting were more common in patients who did not vs did receive ET (21% vs 7%; P = .010).

Study details: This study analyzed the real-world data of 147 patients with HER2+/HR+ metastatic BC from a prospective registry who received first-line chemotherapy plus trastuzumab and pertuzumab with (n = 91) or without (n = 56) concurrent ET.

Disclosures: This study did not receive any funding. Some authors declared serving on the advisory board for or receiving research funding, speaker honoraria, or travel grants from several sources.

Source: Loft M et al. Addition of endocrine therapy to dual anti-HER2 targeted therapy in initial treatment of HER2 + /HR + metastatic breast cancer. Breast Cancer Res Treat. 2023;198:67-74 (Jan 9). Doi: 10.1007/s10549-022-06856-1

Key clinical point: In patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (BC), adding endocrine therapy (ET) to dual anti-HER2 targeted therapy after chemotherapy improved progression-free survival (PFS) without increasing the rate of adverse events.

Major finding: There was a significant improvement in 5-year PFS with vs without the addition of ET (hazard ratio 0.59; P = .031). Nausea and vomiting were more common in patients who did not vs did receive ET (21% vs 7%; P = .010).

Study details: This study analyzed the real-world data of 147 patients with HER2+/HR+ metastatic BC from a prospective registry who received first-line chemotherapy plus trastuzumab and pertuzumab with (n = 91) or without (n = 56) concurrent ET.

Disclosures: This study did not receive any funding. Some authors declared serving on the advisory board for or receiving research funding, speaker honoraria, or travel grants from several sources.

Source: Loft M et al. Addition of endocrine therapy to dual anti-HER2 targeted therapy in initial treatment of HER2 + /HR + metastatic breast cancer. Breast Cancer Res Treat. 2023;198:67-74 (Jan 9). Doi: 10.1007/s10549-022-06856-1

Key clinical point: Marking sentinel lymph nodes (SLN) with superparamagnetic iron oxide (SPIO) nanoparticles led to a substantial proportion of patients with ductal carcinoma in situ (DCIS) of the breast avoiding an upfront SLN dissection (SLND).

Major finding: Upfront SLND could be avoided in 78.3% of patients after marking SLN with SPIO nanoparticles. Among patients receiving delayed SLND, the detection rate was significantly better with SPIO vs radioisotope (⁹⁹Tc), both with (98.2% vs 63.6%) and without the concomitant use of blue dye (92.7% vs 50.9%; both P < .001).

Study details: Findings are from a prospective, multicenter cohort study including 254 patients with DCIS.

Disclosures: This study was funded by the Uppsala University. One author declared serving on an advisory board and receiving institutional grants and speaker honoraria from several sources.

Source: Karakatsanis A et al. Delayed sentinel lymph node dissection in patients with a preoperative diagnosis of ductal cancer in situ by preoperative injection with superparamagnetic iron oxide (SPIO) nanoparticles: The SentiNot study. Ann Surg Oncol. 2023 (Jan 31). Doi: 10.1245/s10434-022-13064-0

Key clinical point: Marking sentinel lymph nodes (SLN) with superparamagnetic iron oxide (SPIO) nanoparticles led to a substantial proportion of patients with ductal carcinoma in situ (DCIS) of the breast avoiding an upfront SLN dissection (SLND).

Major finding: Upfront SLND could be avoided in 78.3% of patients after marking SLN with SPIO nanoparticles. Among patients receiving delayed SLND, the detection rate was significantly better with SPIO vs radioisotope (⁹⁹Tc), both with (98.2% vs 63.6%) and without the concomitant use of blue dye (92.7% vs 50.9%; both P < .001).

Study details: Findings are from a prospective, multicenter cohort study including 254 patients with DCIS.

Disclosures: This study was funded by the Uppsala University. One author declared serving on an advisory board and receiving institutional grants and speaker honoraria from several sources.

Source: Karakatsanis A et al. Delayed sentinel lymph node dissection in patients with a preoperative diagnosis of ductal cancer in situ by preoperative injection with superparamagnetic iron oxide (SPIO) nanoparticles: The SentiNot study. Ann Surg Oncol. 2023 (Jan 31). Doi: 10.1245/s10434-022-13064-0

Key clinical point: Marking sentinel lymph nodes (SLN) with superparamagnetic iron oxide (SPIO) nanoparticles led to a substantial proportion of patients with ductal carcinoma in situ (DCIS) of the breast avoiding an upfront SLN dissection (SLND).

Major finding: Upfront SLND could be avoided in 78.3% of patients after marking SLN with SPIO nanoparticles. Among patients receiving delayed SLND, the detection rate was significantly better with SPIO vs radioisotope (⁹⁹Tc), both with (98.2% vs 63.6%) and without the concomitant use of blue dye (92.7% vs 50.9%; both P < .001).

Study details: Findings are from a prospective, multicenter cohort study including 254 patients with DCIS.

Disclosures: This study was funded by the Uppsala University. One author declared serving on an advisory board and receiving institutional grants and speaker honoraria from several sources.

Source: Karakatsanis A et al. Delayed sentinel lymph node dissection in patients with a preoperative diagnosis of ductal cancer in situ by preoperative injection with superparamagnetic iron oxide (SPIO) nanoparticles: The SentiNot study. Ann Surg Oncol. 2023 (Jan 31). Doi: 10.1245/s10434-022-13064-0

Key clinical point: Contralateral prophylactic mastectomy (CPM) did not offer any survival benefit to patients with triple-negative breast cancer (TNBC) irrespective of the presence of BRCA mutations.

Major finding: The 5-year overall survival did not significantly improve with vs without CPM in the entire population of patients with TNBC (P = .05) and in the subgroups of patients with (P = .35) and without (P = .12) BRCA mutations.

Study details: Findings are from a multi-institutional database study including 796 patients with TNBC, of which 15.5% of patients underwent CPM.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Fasano GA et al. Survival outcomes in women with unilateral, triple-negative, breast cancer correlated with contralateral prophylactic mastectomy. Ann Surg Oncol. 2023 (Jan 21). Doi: 10.1245/s10434-022-13056-0

Key clinical point: Contralateral prophylactic mastectomy (CPM) did not offer any survival benefit to patients with triple-negative breast cancer (TNBC) irrespective of the presence of BRCA mutations.

Major finding: The 5-year overall survival did not significantly improve with vs without CPM in the entire population of patients with TNBC (P = .05) and in the subgroups of patients with (P = .35) and without (P = .12) BRCA mutations.

Study details: Findings are from a multi-institutional database study including 796 patients with TNBC, of which 15.5% of patients underwent CPM.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Fasano GA et al. Survival outcomes in women with unilateral, triple-negative, breast cancer correlated with contralateral prophylactic mastectomy. Ann Surg Oncol. 2023 (Jan 21). Doi: 10.1245/s10434-022-13056-0

Key clinical point: Contralateral prophylactic mastectomy (CPM) did not offer any survival benefit to patients with triple-negative breast cancer (TNBC) irrespective of the presence of BRCA mutations.

Major finding: The 5-year overall survival did not significantly improve with vs without CPM in the entire population of patients with TNBC (P = .05) and in the subgroups of patients with (P = .35) and without (P = .12) BRCA mutations.

Study details: Findings are from a multi-institutional database study including 796 patients with TNBC, of which 15.5% of patients underwent CPM.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Fasano GA et al. Survival outcomes in women with unilateral, triple-negative, breast cancer correlated with contralateral prophylactic mastectomy. Ann Surg Oncol. 2023 (Jan 21). Doi: 10.1245/s10434-022-13056-0

Key clinical point: Adjuvant endocrine therapy (ET) with an aromatase inhibitor (AI) was associated with better disease-free survival (DFS) than tamoxifen-only or tamoxifen+AI in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor2-positive (HER2+) breast cancer (BC).

Major finding: Adjuvant ET with tamoxifen or tamoxifen+AI was associated with significantly worse DFS rates than AI in the entire population of women with HR+/HER2+ BC (hazard ratio 1.64; P = .025), with gonadotropin-releasing hormone being associated with improved DFS rates in premenopausal patients aged ≤45 years (hazard ratio 0.41; P = .023).

Study details: Findings are from a post hoc analysis of the ShortHER trial including 784 patients with HR+/HER2+ early BC who received adjuvant anthracycline/taxane-based chemotherapy plus trastuzumab.

Disclosures: This study was supported by Agenzia Italiana del Farmaco and other sources. Some authors declared receiving personal fees from several sources.

Source: Dieci MV et al. Type of adjuvant endocrine therapy and disease-free survival in patients with early HR-positive/HER2-positive BC: Analysis from the phase III randomized ShortHER trial. NPJ Breast Cancer. 2023;9(1):6 (Feb 4). Doi: 10.1038/s41523-023-00509-2

Key clinical point: Adjuvant endocrine therapy (ET) with an aromatase inhibitor (AI) was associated with better disease-free survival (DFS) than tamoxifen-only or tamoxifen+AI in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor2-positive (HER2+) breast cancer (BC).

Major finding: Adjuvant ET with tamoxifen or tamoxifen+AI was associated with significantly worse DFS rates than AI in the entire population of women with HR+/HER2+ BC (hazard ratio 1.64; P = .025), with gonadotropin-releasing hormone being associated with improved DFS rates in premenopausal patients aged ≤45 years (hazard ratio 0.41; P = .023).

Study details: Findings are from a post hoc analysis of the ShortHER trial including 784 patients with HR+/HER2+ early BC who received adjuvant anthracycline/taxane-based chemotherapy plus trastuzumab.

Disclosures: This study was supported by Agenzia Italiana del Farmaco and other sources. Some authors declared receiving personal fees from several sources.

Source: Dieci MV et al. Type of adjuvant endocrine therapy and disease-free survival in patients with early HR-positive/HER2-positive BC: Analysis from the phase III randomized ShortHER trial. NPJ Breast Cancer. 2023;9(1):6 (Feb 4). Doi: 10.1038/s41523-023-00509-2

Key clinical point: Adjuvant endocrine therapy (ET) with an aromatase inhibitor (AI) was associated with better disease-free survival (DFS) than tamoxifen-only or tamoxifen+AI in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor2-positive (HER2+) breast cancer (BC).

Major finding: Adjuvant ET with tamoxifen or tamoxifen+AI was associated with significantly worse DFS rates than AI in the entire population of women with HR+/HER2+ BC (hazard ratio 1.64; P = .025), with gonadotropin-releasing hormone being associated with improved DFS rates in premenopausal patients aged ≤45 years (hazard ratio 0.41; P = .023).

Study details: Findings are from a post hoc analysis of the ShortHER trial including 784 patients with HR+/HER2+ early BC who received adjuvant anthracycline/taxane-based chemotherapy plus trastuzumab.

Disclosures: This study was supported by Agenzia Italiana del Farmaco and other sources. Some authors declared receiving personal fees from several sources.

Source: Dieci MV et al. Type of adjuvant endocrine therapy and disease-free survival in patients with early HR-positive/HER2-positive BC: Analysis from the phase III randomized ShortHER trial. NPJ Breast Cancer. 2023;9(1):6 (Feb 4). Doi: 10.1038/s41523-023-00509-2

A real-world analysis shows “meaningful” overall survival benefits when a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor is added to endocrine therapy for older women with hormone receptor (HR)–positive/HER2-negative metastatic breast cancer (MBC).

Three years after starting first-line treatment, overall survival rates were 49% with endocrine therapy alone versus 73% with endocrine therapy plus a CDK4/6 inhibitor – findings largely consistent with clinical trial data.

Treatment with endocrine therapy alone “should have a limited role in early lines of therapy for patients with HR-positive/HER2-negative MBC,” the researchers concluded.

The study was published online in the journal Cancer.

The Food and Drug Administration has approved the CDK4/6 inhibitors palbociclib, abemaciclib, and ribociclib for HR-positive/HER2-negative MBC in first and advanced therapy lines. The approval was based on phase 3, randomized, controlled trial data.

Yet gaps in evidence remain regarding survival outcomes in real-world settings for patients starting treatment with a CDK4/6 inhibitor, particularly for patients aged 65 and older, who typically aren’t included in randomized clinical trials.

To address these gaps, Ravi Goyal, PhD, with the University of Houston, and colleagues conducted a retrospective cohort study using the Survey Epidemiology and End Results Medicare database.

Dr. Goyal and coauthors identified 630 Medicare patients with HR-positive/HER2-negative MBC for whom first-line treatment was initiated within 12 months of diagnosis. Patients received either endocrine therapy alone (461 patients) or endocrine therapy plus a CDK4/6 inhibitor (169 patients), most commonly palbociclib.

The median duration of follow-up from the start of treatment was 24 months in the endocrine therapy–alone group and 30 months in the combination therapy group.

In a Kaplan-Meier analysis, the overall survival rate at 3 years after starting first-line treatment was 73% for the combination therapy group versus49% for the endocrine therapy group (P < .0001). Median overall survival from first-line therapy was not estimable in the endocrine therapy plus CDK4/6 inhibitor group; it was 34.8 months in the endocrine therapy–only group.

In multivariable Cox regression models, first-line dual therapy was independently associated with 41% lower rate of death in comparison with endocrine therapy alone (adjusted hazard ratio, 0.59).

Dr. Goyal and colleagues also performed a separate analysis of 206 patients for whom treatment was initiated in the second line; 88 received endocrine therapy alone, and 118 received endocrine therapy plus CDK4/6 inhibitor therapy.

In this setting, a similar benefit of dual therapy was observed. The 3-year overall survival rate was 68% for the combination group versus 50% for endocrine therapy alone (P = .0051). Median overall survival with second-line therapy was not estimable for the combination group; it was 30.9 months for the endocrine therapy group.

In the second line, multivariable Cox regression analysis showed that combination therapy was associated with a nearly 58% lower rate of death in comparison with endocrine therapy alone (aHR, 0.42).

The coauthors of an editorial in Cancer explain that the combination of a CDK4/6 inhibitor and endocrine therapy has become the “preferred first-line approach” in the management of HR-positive/HER2-negative MBC.

Dario Trapani, MD, and Erica Mayer, MD, with Dana-Farber Cancer Institute, Boston, noted that an overall survival benefit of similar magnitude from endocrine therapy plus a CDK4/6 inhibitor has also been reported in a recent real-world study of palbociclib and letrozole.

The work of Dr. Goyal and colleagues provides “confirmatory real-world evidence observed in clinical trials for endocrine sensitive, de novo, metastatic [breast cancer] in an older population,” Dr. Trapani and Dr. Mayer wrote.

The study had no specific funding. The authors and Dr. Trapani disclosed no relevant financial relaitonships. Dr. Mayer has consulted for Lilly, Novartis, Gilead, AstraZeneca, and Diaccurate.

A version of this article first appeared on Medscape.com.

A real-world analysis shows “meaningful” overall survival benefits when a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor is added to endocrine therapy for older women with hormone receptor (HR)–positive/HER2-negative metastatic breast cancer (MBC).

Three years after starting first-line treatment, overall survival rates were 49% with endocrine therapy alone versus 73% with endocrine therapy plus a CDK4/6 inhibitor – findings largely consistent with clinical trial data.

Treatment with endocrine therapy alone “should have a limited role in early lines of therapy for patients with HR-positive/HER2-negative MBC,” the researchers concluded.

The study was published online in the journal Cancer.

The Food and Drug Administration has approved the CDK4/6 inhibitors palbociclib, abemaciclib, and ribociclib for HR-positive/HER2-negative MBC in first and advanced therapy lines. The approval was based on phase 3, randomized, controlled trial data.

Yet gaps in evidence remain regarding survival outcomes in real-world settings for patients starting treatment with a CDK4/6 inhibitor, particularly for patients aged 65 and older, who typically aren’t included in randomized clinical trials.

To address these gaps, Ravi Goyal, PhD, with the University of Houston, and colleagues conducted a retrospective cohort study using the Survey Epidemiology and End Results Medicare database.

Dr. Goyal and coauthors identified 630 Medicare patients with HR-positive/HER2-negative MBC for whom first-line treatment was initiated within 12 months of diagnosis. Patients received either endocrine therapy alone (461 patients) or endocrine therapy plus a CDK4/6 inhibitor (169 patients), most commonly palbociclib.

The median duration of follow-up from the start of treatment was 24 months in the endocrine therapy–alone group and 30 months in the combination therapy group.

In a Kaplan-Meier analysis, the overall survival rate at 3 years after starting first-line treatment was 73% for the combination therapy group versus49% for the endocrine therapy group (P < .0001). Median overall survival from first-line therapy was not estimable in the endocrine therapy plus CDK4/6 inhibitor group; it was 34.8 months in the endocrine therapy–only group.

In multivariable Cox regression models, first-line dual therapy was independently associated with 41% lower rate of death in comparison with endocrine therapy alone (adjusted hazard ratio, 0.59).

Dr. Goyal and colleagues also performed a separate analysis of 206 patients for whom treatment was initiated in the second line; 88 received endocrine therapy alone, and 118 received endocrine therapy plus CDK4/6 inhibitor therapy.

In this setting, a similar benefit of dual therapy was observed. The 3-year overall survival rate was 68% for the combination group versus 50% for endocrine therapy alone (P = .0051). Median overall survival with second-line therapy was not estimable for the combination group; it was 30.9 months for the endocrine therapy group.

In the second line, multivariable Cox regression analysis showed that combination therapy was associated with a nearly 58% lower rate of death in comparison with endocrine therapy alone (aHR, 0.42).

The coauthors of an editorial in Cancer explain that the combination of a CDK4/6 inhibitor and endocrine therapy has become the “preferred first-line approach” in the management of HR-positive/HER2-negative MBC.

Dario Trapani, MD, and Erica Mayer, MD, with Dana-Farber Cancer Institute, Boston, noted that an overall survival benefit of similar magnitude from endocrine therapy plus a CDK4/6 inhibitor has also been reported in a recent real-world study of palbociclib and letrozole.

The work of Dr. Goyal and colleagues provides “confirmatory real-world evidence observed in clinical trials for endocrine sensitive, de novo, metastatic [breast cancer] in an older population,” Dr. Trapani and Dr. Mayer wrote.

The study had no specific funding. The authors and Dr. Trapani disclosed no relevant financial relaitonships. Dr. Mayer has consulted for Lilly, Novartis, Gilead, AstraZeneca, and Diaccurate.

A version of this article first appeared on Medscape.com.

A real-world analysis shows “meaningful” overall survival benefits when a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor is added to endocrine therapy for older women with hormone receptor (HR)–positive/HER2-negative metastatic breast cancer (MBC).

Three years after starting first-line treatment, overall survival rates were 49% with endocrine therapy alone versus 73% with endocrine therapy plus a CDK4/6 inhibitor – findings largely consistent with clinical trial data.

Treatment with endocrine therapy alone “should have a limited role in early lines of therapy for patients with HR-positive/HER2-negative MBC,” the researchers concluded.

The study was published online in the journal Cancer.

The Food and Drug Administration has approved the CDK4/6 inhibitors palbociclib, abemaciclib, and ribociclib for HR-positive/HER2-negative MBC in first and advanced therapy lines. The approval was based on phase 3, randomized, controlled trial data.

Yet gaps in evidence remain regarding survival outcomes in real-world settings for patients starting treatment with a CDK4/6 inhibitor, particularly for patients aged 65 and older, who typically aren’t included in randomized clinical trials.

To address these gaps, Ravi Goyal, PhD, with the University of Houston, and colleagues conducted a retrospective cohort study using the Survey Epidemiology and End Results Medicare database.

Dr. Goyal and coauthors identified 630 Medicare patients with HR-positive/HER2-negative MBC for whom first-line treatment was initiated within 12 months of diagnosis. Patients received either endocrine therapy alone (461 patients) or endocrine therapy plus a CDK4/6 inhibitor (169 patients), most commonly palbociclib.

The median duration of follow-up from the start of treatment was 24 months in the endocrine therapy–alone group and 30 months in the combination therapy group.

In a Kaplan-Meier analysis, the overall survival rate at 3 years after starting first-line treatment was 73% for the combination therapy group versus49% for the endocrine therapy group (P < .0001). Median overall survival from first-line therapy was not estimable in the endocrine therapy plus CDK4/6 inhibitor group; it was 34.8 months in the endocrine therapy–only group.

In multivariable Cox regression models, first-line dual therapy was independently associated with 41% lower rate of death in comparison with endocrine therapy alone (adjusted hazard ratio, 0.59).

Dr. Goyal and colleagues also performed a separate analysis of 206 patients for whom treatment was initiated in the second line; 88 received endocrine therapy alone, and 118 received endocrine therapy plus CDK4/6 inhibitor therapy.

In this setting, a similar benefit of dual therapy was observed. The 3-year overall survival rate was 68% for the combination group versus 50% for endocrine therapy alone (P = .0051). Median overall survival with second-line therapy was not estimable for the combination group; it was 30.9 months for the endocrine therapy group.

In the second line, multivariable Cox regression analysis showed that combination therapy was associated with a nearly 58% lower rate of death in comparison with endocrine therapy alone (aHR, 0.42).

The coauthors of an editorial in Cancer explain that the combination of a CDK4/6 inhibitor and endocrine therapy has become the “preferred first-line approach” in the management of HR-positive/HER2-negative MBC.

Dario Trapani, MD, and Erica Mayer, MD, with Dana-Farber Cancer Institute, Boston, noted that an overall survival benefit of similar magnitude from endocrine therapy plus a CDK4/6 inhibitor has also been reported in a recent real-world study of palbociclib and letrozole.

The work of Dr. Goyal and colleagues provides “confirmatory real-world evidence observed in clinical trials for endocrine sensitive, de novo, metastatic [breast cancer] in an older population,” Dr. Trapani and Dr. Mayer wrote.

The study had no specific funding. The authors and Dr. Trapani disclosed no relevant financial relaitonships. Dr. Mayer has consulted for Lilly, Novartis, Gilead, AstraZeneca, and Diaccurate.

A version of this article first appeared on Medscape.com.

In January 2022, Anthony Arenz, a 51-year-old living in Mesa, Ariz., breathed a small sigh of relief.

The Galleri blood test, which screens for 50 types of cancer, hadn’t detected any positive signs.

It would be welcome news to anyone but especially to a firefighter with a 9% greater risk of developing cancer and a 14% greater risk of dying from it than the average person. The Mesa unit had lost two servicemen to cancer in the past 3 years. Both were more than a decade younger than Mr. Arenz.

When the city of Mesa offered additional free screening – including a full-body MRI – to firefighters over 50, Mr. Arenz initially shrugged it off. With a negative Galleri test in hand, he didn’t want to spend more time dwelling on it.

Still, he began to feel a creeping guilt for skipping a test that many of his fallen colleagues hadn’t been offered. He tried to soothe his anxiety with research. A look through the company’s website didn’t set him at ease. According to Grail Bio, a test result of “no cancer signal detected” does not rule out cancer.

Mr. Arenz booked his free MRI.

The results left him heavy: stage I kidney cancer. The Galleri test had missed it.

Mr. Arenz received his free Galleri test through a cancer screening program funded by the city of Mesa. The program is housed at Vincere Cancer Center in Scottsdale, Ariz. Under the leadership of radiation oncologist and Vincere co-owner Vershalee Shukla, MD, the program currently screens first responders in more than 10 Arizona cities at no cost to them.

Vincere began using Galleri shortly after the test launched for consumers in June 2021. Since then, the first responder program has become the largest commercial user of the test in North America.

But the ability of the Galleri test to identify cancer and, perhaps more importantly, the fallout from erroneous results have been under scrutiny since the test’s launch. The Galleri test, which has not yet been approved by the Food and Drug Administration, is so new that few know what incorrect results look like in practice and how often they might occur.

After running the test on about 2,000 servicemen and servicewomen, Dr. Shukla can offer some insight about the test’s real-world value in a high-risk population.

“Cancer screening is a very complicated issue,” Dr. Shukla said in an interview. “Being honest, the tests are good but are not ready yet [for wider use].”

Mr. Arenz was not the only firefighter who got a surprise after taking a Galleri test.

In nearby Phoenix, 51-year-old firefighter Mike Curtis knew his risk for cancer was high, but he wasn’t that worried. Mr. Curtis had been running into fires since he was 17. His dad, also a firefighter, had died of cancer at age 58.

Mr. Curtis had taken the Vincere Cancer Center up on every free screening service since the program began in late 2018 – well before Dr. Shukla started using Galleri in 2021. His most recent lung CT was clear. But he underwent the Galleri test just to stay vigilant.

His result was a shock. The test detected signs of cancer.

Mr. Curtis decided to tell no one, not even his wife. He’d bear the bad news alone until he was certain.

Dr. Shukla, however, immediately doubted the blood test result. She expedited several follow-up tests. One week, a PET, and CT of the abdomen and pelvis later, her hunch was confirmed. The Galleri test result was wrong, Mr. Curtis did not have cancer.

The price of his peace of mind: an extensive workup with a $4,000 price tag. Fortunately, the bill was covered by the screening program.

Overall, in just over 18 months of using the blood test, Dr. Shukla has only encountered 1 other false positive out of about 2,000 Galleri results.

She also discovered two positive signals for cancer using Galleri that were confirmed with follow-up tests. One was a chordoma, a rare type of bone cancer, and the other was a squamous cell carcinoma of the head and neck. The Galleri test caught both remarkably early, in time for treatment.

For Dr. Shukla, however, false negatives were particularly “horrible.” Mr. Arenz’s was just 1 of 28 cancers that the blood test missed. And because 500 negative tests are yet to be validated, the 28 false negatives may be an underestimate.

In her experience, the binary test result – a simple positive or negative cancer signal – is an oversimplification of risk, she said. It “gives a false perception that you have cancer or you don’t,” although the test itself is not definitive.

Grail senior medical director Whitney Jones, MD, agreed that the test is not meant to be a stand-alone screening test for cancer. The purpose of the Galleri test is to “complement other screenings, not replace them,” Dr. Jones told this news organization.

According to an analysis of Galleri data and Dr. Shukla’s experience, the test’s specificity was over 99%. That means the test successfully minimizes false positives.

But the test’s sensitivity was much lower. From data from first responders, Dr. Shukla determined the sensitivity to be 6.7%. That means the test misses about 93 of every 100 cancers. According to Grail’s latest data from more than 6,300 people older than 50, the test’s sensitivity was 29%.

Specificity and sensitivity are metrics used to credential a test and establish confidence in its ability to detect the target disease. A test with high specificity can correctly identify patients who do not have the condition in question, while a test with high sensitivity can correctly identify patients who do have the disease. But there are trade-offs between sensitivity and specificity. One value is increased at the expense of the other.

It’s normal for a cancer screening test to prioritize specificity, according to Aparna Parikh, MD, an oncologist at Mass General Cancer Center in Boston. In a test like Galleri, which is meant to be an adjunct to other screening modalities, “at least we are seeing a good specificity, which is important, because we don’t want false positives, where the downstream impact on the patient can be high.”

Overall, Dr. Jones said, Grail Bio’s aim is to build a test that’s sensitive enough to catch the most dangerous cancers without inundating the healthcare system with false positives. In addition, Dr. Jones explained, sensitivity varies by cancer type. It tends to be lower for cancers for which other screening modalities are available, as well as for earlier-stage disease.

However, the Galleri sensitivity values are “a little bit scary,” said Ji-Hyun Lee, DrPH, professor of biostatistics at the University of Florida and director of the division of quantitative sciences at the University of Florida Health Cancer Center, both in Gainesville. Dr. Lee, who is not affiliated with Grail, reviewed the company’s publicly available data as well as Dr. Shukla’s data at the request of this news organization.

While there’s no definitive threshold for sensitivity, miss rates as high as 93% and 71% “provide little confidence in the [accuracy of the] test,” Dr. Lee said.

Positive and negative predictive values, however, are more clinically relevant measures of a screening test. These numbers indicate how likely it is that a patient’s results are true and therefore how worried they should be about a positive result and how much they should trust a negative result.

Galleri’s data in the over-50 population and Dr. Shukla’s in first responders suggest the test’s negative predictive value is very high – 98.6% and 98.1%, respectively – which means most people can trust a negative test result.

The positive predictive value, however, was less straightforward. In first responders, Dr. Shukla found that only half of positive Galleri tests were confirmed cases of cancer. And an analysis of Grail’s data found that only 38% of positive Galleri tests – 35 of 92 tests – represented a validated cancer diagnosis.

“In a clinical setting, positive predictive value is more usable for decision-making for the patient,” said Dr. Lee. “Positive predictive value isn’t always high, because everything doesn’t always transfer perfectly to the clinic.” But in the general population, if only 38% of patients with positive Galleri results truly have cancer, the test is “not quite useful to make a decision for the patient or the providers.”

Galleri may also be a costly prospect for patients, no matter the result, cautioned Electra Paskett, PhD, an epidemiologist and cancer screening expert at Ohio State University, Columbus. A positive Galleri test leads to a cascade of follow-up diagnostic tests, which payers may not cover. For a negative result, Galleri recommends that the patient undergo screening again in a year, at an annual cost of $950 plus the cost of any follow-up testing when Galleri does pick something up.

“If a provider wants to offer the Galleri test, all those things need to be made abundantly clear, in my opinion,” Dr. Paskett said.

Following the negative Galleri test, Mr. Arenz’s cancer didn’t slip through the cracks because he received other advanced imaging free of charge. But whether all doctors will go to such lengths to back up Galleri results, even for patients with negative results, is unknown.

A negative result can give patients “a huge false sense of security,” said Dr. Shukla. And if a test is positive, the workup isn’t simple. Chasing cancer, especially one that’s not really there, can be nerve-wracking and expensive.

The question, then, is why perform the Galleri test at all if results require so much validation?

Dr. Parikh explained that a high-risk group such as firefighters represents an ideal-use case for Galleri and other liquid biopsy tests. But she noted that she would be “wary of the ability of the system to manage this test en masse” were the test to be used more widely in the general population.

Dr. Shukla said it’s less about the results she’s getting today and more about making the test more effective for her patients in the future. First responders need a test such as this that can quickly identify multiple cancers. However, to improve the test, Grail needs more data from this high-risk population. That’s what she’s after.

Mr. Curtis doesn’t regret taking the Galleri test. The emotional toll of thinking he had cancer for a few days wasn’t too high a price, in his opinion. It’s part of cancer screening. But he acknowledged that it would have been a much more burdensome experience had he’d been financially responsible for the workup or if he hadn’t had Dr. Shukla to manage his case from start to finish.

Because it was free, Mr. Arenz doesn’t regret undergoing the Galleri test either. But he tells his coworkers to check the site, do their research, and get more screening.

“Any medical center that’s just doing this one test, you just have to be careful,” Dr. Shukla said. “It’s not that easy.”

A version of this article first appeared on Medscape.com.

In January 2022, Anthony Arenz, a 51-year-old living in Mesa, Ariz., breathed a small sigh of relief.

The Galleri blood test, which screens for 50 types of cancer, hadn’t detected any positive signs.

It would be welcome news to anyone but especially to a firefighter with a 9% greater risk of developing cancer and a 14% greater risk of dying from it than the average person. The Mesa unit had lost two servicemen to cancer in the past 3 years. Both were more than a decade younger than Mr. Arenz.

When the city of Mesa offered additional free screening – including a full-body MRI – to firefighters over 50, Mr. Arenz initially shrugged it off. With a negative Galleri test in hand, he didn’t want to spend more time dwelling on it.

Still, he began to feel a creeping guilt for skipping a test that many of his fallen colleagues hadn’t been offered. He tried to soothe his anxiety with research. A look through the company’s website didn’t set him at ease. According to Grail Bio, a test result of “no cancer signal detected” does not rule out cancer.

Mr. Arenz booked his free MRI.

The results left him heavy: stage I kidney cancer. The Galleri test had missed it.

Mr. Arenz received his free Galleri test through a cancer screening program funded by the city of Mesa. The program is housed at Vincere Cancer Center in Scottsdale, Ariz. Under the leadership of radiation oncologist and Vincere co-owner Vershalee Shukla, MD, the program currently screens first responders in more than 10 Arizona cities at no cost to them.

Vincere began using Galleri shortly after the test launched for consumers in June 2021. Since then, the first responder program has become the largest commercial user of the test in North America.

But the ability of the Galleri test to identify cancer and, perhaps more importantly, the fallout from erroneous results have been under scrutiny since the test’s launch. The Galleri test, which has not yet been approved by the Food and Drug Administration, is so new that few know what incorrect results look like in practice and how often they might occur.

After running the test on about 2,000 servicemen and servicewomen, Dr. Shukla can offer some insight about the test’s real-world value in a high-risk population.

“Cancer screening is a very complicated issue,” Dr. Shukla said in an interview. “Being honest, the tests are good but are not ready yet [for wider use].”

Mr. Arenz was not the only firefighter who got a surprise after taking a Galleri test.

In nearby Phoenix, 51-year-old firefighter Mike Curtis knew his risk for cancer was high, but he wasn’t that worried. Mr. Curtis had been running into fires since he was 17. His dad, also a firefighter, had died of cancer at age 58.

Mr. Curtis had taken the Vincere Cancer Center up on every free screening service since the program began in late 2018 – well before Dr. Shukla started using Galleri in 2021. His most recent lung CT was clear. But he underwent the Galleri test just to stay vigilant.

His result was a shock. The test detected signs of cancer.

Mr. Curtis decided to tell no one, not even his wife. He’d bear the bad news alone until he was certain.

Dr. Shukla, however, immediately doubted the blood test result. She expedited several follow-up tests. One week, a PET, and CT of the abdomen and pelvis later, her hunch was confirmed. The Galleri test result was wrong, Mr. Curtis did not have cancer.

The price of his peace of mind: an extensive workup with a $4,000 price tag. Fortunately, the bill was covered by the screening program.

Overall, in just over 18 months of using the blood test, Dr. Shukla has only encountered 1 other false positive out of about 2,000 Galleri results.

She also discovered two positive signals for cancer using Galleri that were confirmed with follow-up tests. One was a chordoma, a rare type of bone cancer, and the other was a squamous cell carcinoma of the head and neck. The Galleri test caught both remarkably early, in time for treatment.

For Dr. Shukla, however, false negatives were particularly “horrible.” Mr. Arenz’s was just 1 of 28 cancers that the blood test missed. And because 500 negative tests are yet to be validated, the 28 false negatives may be an underestimate.

In her experience, the binary test result – a simple positive or negative cancer signal – is an oversimplification of risk, she said. It “gives a false perception that you have cancer or you don’t,” although the test itself is not definitive.

Grail senior medical director Whitney Jones, MD, agreed that the test is not meant to be a stand-alone screening test for cancer. The purpose of the Galleri test is to “complement other screenings, not replace them,” Dr. Jones told this news organization.

According to an analysis of Galleri data and Dr. Shukla’s experience, the test’s specificity was over 99%. That means the test successfully minimizes false positives.

But the test’s sensitivity was much lower. From data from first responders, Dr. Shukla determined the sensitivity to be 6.7%. That means the test misses about 93 of every 100 cancers. According to Grail’s latest data from more than 6,300 people older than 50, the test’s sensitivity was 29%.

Specificity and sensitivity are metrics used to credential a test and establish confidence in its ability to detect the target disease. A test with high specificity can correctly identify patients who do not have the condition in question, while a test with high sensitivity can correctly identify patients who do have the disease. But there are trade-offs between sensitivity and specificity. One value is increased at the expense of the other.

It’s normal for a cancer screening test to prioritize specificity, according to Aparna Parikh, MD, an oncologist at Mass General Cancer Center in Boston. In a test like Galleri, which is meant to be an adjunct to other screening modalities, “at least we are seeing a good specificity, which is important, because we don’t want false positives, where the downstream impact on the patient can be high.”

Overall, Dr. Jones said, Grail Bio’s aim is to build a test that’s sensitive enough to catch the most dangerous cancers without inundating the healthcare system with false positives. In addition, Dr. Jones explained, sensitivity varies by cancer type. It tends to be lower for cancers for which other screening modalities are available, as well as for earlier-stage disease.

However, the Galleri sensitivity values are “a little bit scary,” said Ji-Hyun Lee, DrPH, professor of biostatistics at the University of Florida and director of the division of quantitative sciences at the University of Florida Health Cancer Center, both in Gainesville. Dr. Lee, who is not affiliated with Grail, reviewed the company’s publicly available data as well as Dr. Shukla’s data at the request of this news organization.

While there’s no definitive threshold for sensitivity, miss rates as high as 93% and 71% “provide little confidence in the [accuracy of the] test,” Dr. Lee said.

Positive and negative predictive values, however, are more clinically relevant measures of a screening test. These numbers indicate how likely it is that a patient’s results are true and therefore how worried they should be about a positive result and how much they should trust a negative result.

Galleri’s data in the over-50 population and Dr. Shukla’s in first responders suggest the test’s negative predictive value is very high – 98.6% and 98.1%, respectively – which means most people can trust a negative test result.

The positive predictive value, however, was less straightforward. In first responders, Dr. Shukla found that only half of positive Galleri tests were confirmed cases of cancer. And an analysis of Grail’s data found that only 38% of positive Galleri tests – 35 of 92 tests – represented a validated cancer diagnosis.

“In a clinical setting, positive predictive value is more usable for decision-making for the patient,” said Dr. Lee. “Positive predictive value isn’t always high, because everything doesn’t always transfer perfectly to the clinic.” But in the general population, if only 38% of patients with positive Galleri results truly have cancer, the test is “not quite useful to make a decision for the patient or the providers.”

Galleri may also be a costly prospect for patients, no matter the result, cautioned Electra Paskett, PhD, an epidemiologist and cancer screening expert at Ohio State University, Columbus. A positive Galleri test leads to a cascade of follow-up diagnostic tests, which payers may not cover. For a negative result, Galleri recommends that the patient undergo screening again in a year, at an annual cost of $950 plus the cost of any follow-up testing when Galleri does pick something up.

“If a provider wants to offer the Galleri test, all those things need to be made abundantly clear, in my opinion,” Dr. Paskett said.

Following the negative Galleri test, Mr. Arenz’s cancer didn’t slip through the cracks because he received other advanced imaging free of charge. But whether all doctors will go to such lengths to back up Galleri results, even for patients with negative results, is unknown.

A negative result can give patients “a huge false sense of security,” said Dr. Shukla. And if a test is positive, the workup isn’t simple. Chasing cancer, especially one that’s not really there, can be nerve-wracking and expensive.

The question, then, is why perform the Galleri test at all if results require so much validation?

Dr. Parikh explained that a high-risk group such as firefighters represents an ideal-use case for Galleri and other liquid biopsy tests. But she noted that she would be “wary of the ability of the system to manage this test en masse” were the test to be used more widely in the general population.

Dr. Shukla said it’s less about the results she’s getting today and more about making the test more effective for her patients in the future. First responders need a test such as this that can quickly identify multiple cancers. However, to improve the test, Grail needs more data from this high-risk population. That’s what she’s after.

Mr. Curtis doesn’t regret taking the Galleri test. The emotional toll of thinking he had cancer for a few days wasn’t too high a price, in his opinion. It’s part of cancer screening. But he acknowledged that it would have been a much more burdensome experience had he’d been financially responsible for the workup or if he hadn’t had Dr. Shukla to manage his case from start to finish.

Because it was free, Mr. Arenz doesn’t regret undergoing the Galleri test either. But he tells his coworkers to check the site, do their research, and get more screening.

“Any medical center that’s just doing this one test, you just have to be careful,” Dr. Shukla said. “It’s not that easy.”

A version of this article first appeared on Medscape.com.

In January 2022, Anthony Arenz, a 51-year-old living in Mesa, Ariz., breathed a small sigh of relief.

The Galleri blood test, which screens for 50 types of cancer, hadn’t detected any positive signs.

It would be welcome news to anyone but especially to a firefighter with a 9% greater risk of developing cancer and a 14% greater risk of dying from it than the average person. The Mesa unit had lost two servicemen to cancer in the past 3 years. Both were more than a decade younger than Mr. Arenz.

When the city of Mesa offered additional free screening – including a full-body MRI – to firefighters over 50, Mr. Arenz initially shrugged it off. With a negative Galleri test in hand, he didn’t want to spend more time dwelling on it.

Still, he began to feel a creeping guilt for skipping a test that many of his fallen colleagues hadn’t been offered. He tried to soothe his anxiety with research. A look through the company’s website didn’t set him at ease. According to Grail Bio, a test result of “no cancer signal detected” does not rule out cancer.

Mr. Arenz booked his free MRI.

The results left him heavy: stage I kidney cancer. The Galleri test had missed it.

Mr. Arenz received his free Galleri test through a cancer screening program funded by the city of Mesa. The program is housed at Vincere Cancer Center in Scottsdale, Ariz. Under the leadership of radiation oncologist and Vincere co-owner Vershalee Shukla, MD, the program currently screens first responders in more than 10 Arizona cities at no cost to them.

Vincere began using Galleri shortly after the test launched for consumers in June 2021. Since then, the first responder program has become the largest commercial user of the test in North America.

But the ability of the Galleri test to identify cancer and, perhaps more importantly, the fallout from erroneous results have been under scrutiny since the test’s launch. The Galleri test, which has not yet been approved by the Food and Drug Administration, is so new that few know what incorrect results look like in practice and how often they might occur.

After running the test on about 2,000 servicemen and servicewomen, Dr. Shukla can offer some insight about the test’s real-world value in a high-risk population.

“Cancer screening is a very complicated issue,” Dr. Shukla said in an interview. “Being honest, the tests are good but are not ready yet [for wider use].”

Mr. Arenz was not the only firefighter who got a surprise after taking a Galleri test.

In nearby Phoenix, 51-year-old firefighter Mike Curtis knew his risk for cancer was high, but he wasn’t that worried. Mr. Curtis had been running into fires since he was 17. His dad, also a firefighter, had died of cancer at age 58.

Mr. Curtis had taken the Vincere Cancer Center up on every free screening service since the program began in late 2018 – well before Dr. Shukla started using Galleri in 2021. His most recent lung CT was clear. But he underwent the Galleri test just to stay vigilant.

His result was a shock. The test detected signs of cancer.

Mr. Curtis decided to tell no one, not even his wife. He’d bear the bad news alone until he was certain.

Dr. Shukla, however, immediately doubted the blood test result. She expedited several follow-up tests. One week, a PET, and CT of the abdomen and pelvis later, her hunch was confirmed. The Galleri test result was wrong, Mr. Curtis did not have cancer.

The price of his peace of mind: an extensive workup with a $4,000 price tag. Fortunately, the bill was covered by the screening program.

Overall, in just over 18 months of using the blood test, Dr. Shukla has only encountered 1 other false positive out of about 2,000 Galleri results.

She also discovered two positive signals for cancer using Galleri that were confirmed with follow-up tests. One was a chordoma, a rare type of bone cancer, and the other was a squamous cell carcinoma of the head and neck. The Galleri test caught both remarkably early, in time for treatment.

For Dr. Shukla, however, false negatives were particularly “horrible.” Mr. Arenz’s was just 1 of 28 cancers that the blood test missed. And because 500 negative tests are yet to be validated, the 28 false negatives may be an underestimate.

In her experience, the binary test result – a simple positive or negative cancer signal – is an oversimplification of risk, she said. It “gives a false perception that you have cancer or you don’t,” although the test itself is not definitive.

Grail senior medical director Whitney Jones, MD, agreed that the test is not meant to be a stand-alone screening test for cancer. The purpose of the Galleri test is to “complement other screenings, not replace them,” Dr. Jones told this news organization.

According to an analysis of Galleri data and Dr. Shukla’s experience, the test’s specificity was over 99%. That means the test successfully minimizes false positives.

But the test’s sensitivity was much lower. From data from first responders, Dr. Shukla determined the sensitivity to be 6.7%. That means the test misses about 93 of every 100 cancers. According to Grail’s latest data from more than 6,300 people older than 50, the test’s sensitivity was 29%.

Specificity and sensitivity are metrics used to credential a test and establish confidence in its ability to detect the target disease. A test with high specificity can correctly identify patients who do not have the condition in question, while a test with high sensitivity can correctly identify patients who do have the disease. But there are trade-offs between sensitivity and specificity. One value is increased at the expense of the other.

It’s normal for a cancer screening test to prioritize specificity, according to Aparna Parikh, MD, an oncologist at Mass General Cancer Center in Boston. In a test like Galleri, which is meant to be an adjunct to other screening modalities, “at least we are seeing a good specificity, which is important, because we don’t want false positives, where the downstream impact on the patient can be high.”

Overall, Dr. Jones said, Grail Bio’s aim is to build a test that’s sensitive enough to catch the most dangerous cancers without inundating the healthcare system with false positives. In addition, Dr. Jones explained, sensitivity varies by cancer type. It tends to be lower for cancers for which other screening modalities are available, as well as for earlier-stage disease.

However, the Galleri sensitivity values are “a little bit scary,” said Ji-Hyun Lee, DrPH, professor of biostatistics at the University of Florida and director of the division of quantitative sciences at the University of Florida Health Cancer Center, both in Gainesville. Dr. Lee, who is not affiliated with Grail, reviewed the company’s publicly available data as well as Dr. Shukla’s data at the request of this news organization.

While there’s no definitive threshold for sensitivity, miss rates as high as 93% and 71% “provide little confidence in the [accuracy of the] test,” Dr. Lee said.

Positive and negative predictive values, however, are more clinically relevant measures of a screening test. These numbers indicate how likely it is that a patient’s results are true and therefore how worried they should be about a positive result and how much they should trust a negative result.

Galleri’s data in the over-50 population and Dr. Shukla’s in first responders suggest the test’s negative predictive value is very high – 98.6% and 98.1%, respectively – which means most people can trust a negative test result.

The positive predictive value, however, was less straightforward. In first responders, Dr. Shukla found that only half of positive Galleri tests were confirmed cases of cancer. And an analysis of Grail’s data found that only 38% of positive Galleri tests – 35 of 92 tests – represented a validated cancer diagnosis.

“In a clinical setting, positive predictive value is more usable for decision-making for the patient,” said Dr. Lee. “Positive predictive value isn’t always high, because everything doesn’t always transfer perfectly to the clinic.” But in the general population, if only 38% of patients with positive Galleri results truly have cancer, the test is “not quite useful to make a decision for the patient or the providers.”

Galleri may also be a costly prospect for patients, no matter the result, cautioned Electra Paskett, PhD, an epidemiologist and cancer screening expert at Ohio State University, Columbus. A positive Galleri test leads to a cascade of follow-up diagnostic tests, which payers may not cover. For a negative result, Galleri recommends that the patient undergo screening again in a year, at an annual cost of $950 plus the cost of any follow-up testing when Galleri does pick something up.

“If a provider wants to offer the Galleri test, all those things need to be made abundantly clear, in my opinion,” Dr. Paskett said.

Following the negative Galleri test, Mr. Arenz’s cancer didn’t slip through the cracks because he received other advanced imaging free of charge. But whether all doctors will go to such lengths to back up Galleri results, even for patients with negative results, is unknown.

A negative result can give patients “a huge false sense of security,” said Dr. Shukla. And if a test is positive, the workup isn’t simple. Chasing cancer, especially one that’s not really there, can be nerve-wracking and expensive.

The question, then, is why perform the Galleri test at all if results require so much validation?

Dr. Parikh explained that a high-risk group such as firefighters represents an ideal-use case for Galleri and other liquid biopsy tests. But she noted that she would be “wary of the ability of the system to manage this test en masse” were the test to be used more widely in the general population.

Dr. Shukla said it’s less about the results she’s getting today and more about making the test more effective for her patients in the future. First responders need a test such as this that can quickly identify multiple cancers. However, to improve the test, Grail needs more data from this high-risk population. That’s what she’s after.

Mr. Curtis doesn’t regret taking the Galleri test. The emotional toll of thinking he had cancer for a few days wasn’t too high a price, in his opinion. It’s part of cancer screening. But he acknowledged that it would have been a much more burdensome experience had he’d been financially responsible for the workup or if he hadn’t had Dr. Shukla to manage his case from start to finish.

Because it was free, Mr. Arenz doesn’t regret undergoing the Galleri test either. But he tells his coworkers to check the site, do their research, and get more screening.

“Any medical center that’s just doing this one test, you just have to be careful,” Dr. Shukla said. “It’s not that easy.”

A version of this article first appeared on Medscape.com.

Women across the world face high levels of financial burden from breast cancer, a new systematic review and analysis finds. While the burden of the disease is much higher in less-developed countries, about a third of women in Western nations like the United States say the disease has hurt their financial well-being.

When it comes to financial burden, patients with breast cancer are “a highly vulnerable patient population,” said study coauthor Kavitha Ranganathan, MD, of Brigham and Women’s Hospital, Boston, in an interview. “We need to be both strategic and comprehensive with our approach and use evidence-based methods to come up with these comprehensive solutions,” said Dr. Ranganathan, who noted that she’s hearing more from patients who face monetary hurdles.

The findings were published online in JAMA Network Open.

The researchers believe their analysis is the first to attempt to understand financial toxicity (FT) – excessive financial burden – in breast cancer on a global level. This turned out to be a challenge since there’s no standard way to measure FT.

One approach is to look at financial burden in terms of whether patients are suffering from “catastrophic expenditure,” Dr. Ranganathan said. “That’s what the World Bank and other top health and economic organizations have focused on. It means that the cost of care and – whatever it takes to get care – exceeds 10% of total annual household income.”

Another approach is more subjective and based on patient-reported outcomes, she said: “Are patients having to forgo basic subsistence needs like rent and food?”

For the report, researchers analyzed studies that use both approaches to measure FT from breast cancer. The studies came from high-income countries (n = 24, including 19 from the United States) and middle- and low-income countries (n = 10), and ranged in size from 5 to 2,445 subjects.

The analyzed studies were a range of cross-sectional (n = 26), prospective (n = 7), and retrospective designs (n = 1).

The authors pooled the data from 18 studies and estimated that the rate of patients with FT was 35.3% (14 studies, 27.3%-44.4%) in high-income countries and 78.8% (4 studies, 60.4%-90.0%) in the other countries.

The researchers also conducted a separate pooled analysis of only the U.S. studies (n = 11). It found that 34% (27%-43%) of subjects reported FT. The researchers also conducted a new analysis of Canada-only studies (n = 2) and found that 19% (9%-35%) reported FT.

The researchers weren’t able to provide insight into trends in FT in the United States prior to the period of the studies (2014-2021). But raw numbers suggest the percentage of patients facing financial challenges rose over that time, suggesting a possible increase in burden.

Previous research has suggested that breast cancer poses a higher financial burden than other chronic conditions. “Breast cancer care in particular may be associated with high FT given the need for screening and diagnosis, multidisciplinary care, and longitudinal follow-up,” the researchers write. They add that “notably, gender also affects financial security.”

As for limitations, the researchers report that they only analyzed studies in English, and there was a wide variation in approaches used to analyze FT. The analysis “did not account for different health care systems or control for health care–dedicated gross domestic product,” meaning that there’s no way to know for sure that rates were lower in nations with universal health care.

How could the new findings be useful? “They’re eye-opening for health policymakers. Whenever they see these numbers, they will say, ‘Wow, it is really a problem,’ and they’ll start thinking about solutions,” said study coauthor Rania A. Mekary, PhD, MSc, MSc, of Massachusetts College of Pharmacy and Health Sciences in Boston. “When you give them evidence-based data, then they will take it more seriously.”

The researchers call for interventions in several areas including education about early diagnosis and treatment of breast cancer, expansion of health care coverage, programs to help with nonmedical costs, and better resources for breast cancer care.

In an interview, Mary C. Politi, PhD, of Washington University, St. Louis, said the new report is useful “because it examines financial hardship internationally. Some people wonder whether financial hardship is a U.S. problem because of our health care system, which often relies on insurance and a lot of cost-sharing between insurance and patients. However, financial toxicity is prevalent across countries.”

And, she said, “the study is also useful because it encourages us to measure financial hardship and burden in a more uniform way so we can better compare and pool studies.”

Dr. Politi noted that there are ways to help patients now. “Most hospitals and health centers have staff who can talk to patients about their bills. Sometimes, a payment plan can be set up to space out payments,” she said. “Health care teams can try to consolidate care for patients on the same day to reduce parking expenses or time off for work or child care. Sometimes, changing to less expensive but effective generic medications is an option.”

The study authors received support from the National Cancer Institute, the United Nations Institute for Training and Research, the Global Surgery Foundation, the Harvard Global Health Institute, the Connors Center for Women’s Health and Gender Biology, the Center for Surgery and Public Health, and the National Endowment for Plastic Surgery. Dr. Ranganathan and Dr. Mekary report no disclosures. One coauthor reported a patent (BREAST-Q) and codevelopment of QPROMS, owned by Memorial Sloan Kettering Cancer Center. Another author reports salary support from Blue Cross Blue Shield of Michigan through the collaborative quality initiative known as Michigan Social Health Interventions to Eliminate Disparities. Dr. Politi has no disclosures.

Women across the world face high levels of financial burden from breast cancer, a new systematic review and analysis finds. While the burden of the disease is much higher in less-developed countries, about a third of women in Western nations like the United States say the disease has hurt their financial well-being.

When it comes to financial burden, patients with breast cancer are “a highly vulnerable patient population,” said study coauthor Kavitha Ranganathan, MD, of Brigham and Women’s Hospital, Boston, in an interview. “We need to be both strategic and comprehensive with our approach and use evidence-based methods to come up with these comprehensive solutions,” said Dr. Ranganathan, who noted that she’s hearing more from patients who face monetary hurdles.

The findings were published online in JAMA Network Open.

The researchers believe their analysis is the first to attempt to understand financial toxicity (FT) – excessive financial burden – in breast cancer on a global level. This turned out to be a challenge since there’s no standard way to measure FT.

One approach is to look at financial burden in terms of whether patients are suffering from “catastrophic expenditure,” Dr. Ranganathan said. “That’s what the World Bank and other top health and economic organizations have focused on. It means that the cost of care and – whatever it takes to get care – exceeds 10% of total annual household income.”

Another approach is more subjective and based on patient-reported outcomes, she said: “Are patients having to forgo basic subsistence needs like rent and food?”

For the report, researchers analyzed studies that use both approaches to measure FT from breast cancer. The studies came from high-income countries (n = 24, including 19 from the United States) and middle- and low-income countries (n = 10), and ranged in size from 5 to 2,445 subjects.

The analyzed studies were a range of cross-sectional (n = 26), prospective (n = 7), and retrospective designs (n = 1).

The authors pooled the data from 18 studies and estimated that the rate of patients with FT was 35.3% (14 studies, 27.3%-44.4%) in high-income countries and 78.8% (4 studies, 60.4%-90.0%) in the other countries.

The researchers also conducted a separate pooled analysis of only the U.S. studies (n = 11). It found that 34% (27%-43%) of subjects reported FT. The researchers also conducted a new analysis of Canada-only studies (n = 2) and found that 19% (9%-35%) reported FT.

The researchers weren’t able to provide insight into trends in FT in the United States prior to the period of the studies (2014-2021). But raw numbers suggest the percentage of patients facing financial challenges rose over that time, suggesting a possible increase in burden.

Previous research has suggested that breast cancer poses a higher financial burden than other chronic conditions. “Breast cancer care in particular may be associated with high FT given the need for screening and diagnosis, multidisciplinary care, and longitudinal follow-up,” the researchers write. They add that “notably, gender also affects financial security.”

As for limitations, the researchers report that they only analyzed studies in English, and there was a wide variation in approaches used to analyze FT. The analysis “did not account for different health care systems or control for health care–dedicated gross domestic product,” meaning that there’s no way to know for sure that rates were lower in nations with universal health care.

How could the new findings be useful? “They’re eye-opening for health policymakers. Whenever they see these numbers, they will say, ‘Wow, it is really a problem,’ and they’ll start thinking about solutions,” said study coauthor Rania A. Mekary, PhD, MSc, MSc, of Massachusetts College of Pharmacy and Health Sciences in Boston. “When you give them evidence-based data, then they will take it more seriously.”

The researchers call for interventions in several areas including education about early diagnosis and treatment of breast cancer, expansion of health care coverage, programs to help with nonmedical costs, and better resources for breast cancer care.

In an interview, Mary C. Politi, PhD, of Washington University, St. Louis, said the new report is useful “because it examines financial hardship internationally. Some people wonder whether financial hardship is a U.S. problem because of our health care system, which often relies on insurance and a lot of cost-sharing between insurance and patients. However, financial toxicity is prevalent across countries.”

And, she said, “the study is also useful because it encourages us to measure financial hardship and burden in a more uniform way so we can better compare and pool studies.”

Dr. Politi noted that there are ways to help patients now. “Most hospitals and health centers have staff who can talk to patients about their bills. Sometimes, a payment plan can be set up to space out payments,” she said. “Health care teams can try to consolidate care for patients on the same day to reduce parking expenses or time off for work or child care. Sometimes, changing to less expensive but effective generic medications is an option.”

The study authors received support from the National Cancer Institute, the United Nations Institute for Training and Research, the Global Surgery Foundation, the Harvard Global Health Institute, the Connors Center for Women’s Health and Gender Biology, the Center for Surgery and Public Health, and the National Endowment for Plastic Surgery. Dr. Ranganathan and Dr. Mekary report no disclosures. One coauthor reported a patent (BREAST-Q) and codevelopment of QPROMS, owned by Memorial Sloan Kettering Cancer Center. Another author reports salary support from Blue Cross Blue Shield of Michigan through the collaborative quality initiative known as Michigan Social Health Interventions to Eliminate Disparities. Dr. Politi has no disclosures.

Women across the world face high levels of financial burden from breast cancer, a new systematic review and analysis finds. While the burden of the disease is much higher in less-developed countries, about a third of women in Western nations like the United States say the disease has hurt their financial well-being.

When it comes to financial burden, patients with breast cancer are “a highly vulnerable patient population,” said study coauthor Kavitha Ranganathan, MD, of Brigham and Women’s Hospital, Boston, in an interview. “We need to be both strategic and comprehensive with our approach and use evidence-based methods to come up with these comprehensive solutions,” said Dr. Ranganathan, who noted that she’s hearing more from patients who face monetary hurdles.

The findings were published online in JAMA Network Open.

The researchers believe their analysis is the first to attempt to understand financial toxicity (FT) – excessive financial burden – in breast cancer on a global level. This turned out to be a challenge since there’s no standard way to measure FT.

One approach is to look at financial burden in terms of whether patients are suffering from “catastrophic expenditure,” Dr. Ranganathan said. “That’s what the World Bank and other top health and economic organizations have focused on. It means that the cost of care and – whatever it takes to get care – exceeds 10% of total annual household income.”

Another approach is more subjective and based on patient-reported outcomes, she said: “Are patients having to forgo basic subsistence needs like rent and food?”

For the report, researchers analyzed studies that use both approaches to measure FT from breast cancer. The studies came from high-income countries (n = 24, including 19 from the United States) and middle- and low-income countries (n = 10), and ranged in size from 5 to 2,445 subjects.

The analyzed studies were a range of cross-sectional (n = 26), prospective (n = 7), and retrospective designs (n = 1).

The authors pooled the data from 18 studies and estimated that the rate of patients with FT was 35.3% (14 studies, 27.3%-44.4%) in high-income countries and 78.8% (4 studies, 60.4%-90.0%) in the other countries.

The researchers also conducted a separate pooled analysis of only the U.S. studies (n = 11). It found that 34% (27%-43%) of subjects reported FT. The researchers also conducted a new analysis of Canada-only studies (n = 2) and found that 19% (9%-35%) reported FT.

The researchers weren’t able to provide insight into trends in FT in the United States prior to the period of the studies (2014-2021). But raw numbers suggest the percentage of patients facing financial challenges rose over that time, suggesting a possible increase in burden.

Previous research has suggested that breast cancer poses a higher financial burden than other chronic conditions. “Breast cancer care in particular may be associated with high FT given the need for screening and diagnosis, multidisciplinary care, and longitudinal follow-up,” the researchers write. They add that “notably, gender also affects financial security.”

As for limitations, the researchers report that they only analyzed studies in English, and there was a wide variation in approaches used to analyze FT. The analysis “did not account for different health care systems or control for health care–dedicated gross domestic product,” meaning that there’s no way to know for sure that rates were lower in nations with universal health care.

How could the new findings be useful? “They’re eye-opening for health policymakers. Whenever they see these numbers, they will say, ‘Wow, it is really a problem,’ and they’ll start thinking about solutions,” said study coauthor Rania A. Mekary, PhD, MSc, MSc, of Massachusetts College of Pharmacy and Health Sciences in Boston. “When you give them evidence-based data, then they will take it more seriously.”

The researchers call for interventions in several areas including education about early diagnosis and treatment of breast cancer, expansion of health care coverage, programs to help with nonmedical costs, and better resources for breast cancer care.

In an interview, Mary C. Politi, PhD, of Washington University, St. Louis, said the new report is useful “because it examines financial hardship internationally. Some people wonder whether financial hardship is a U.S. problem because of our health care system, which often relies on insurance and a lot of cost-sharing between insurance and patients. However, financial toxicity is prevalent across countries.”

And, she said, “the study is also useful because it encourages us to measure financial hardship and burden in a more uniform way so we can better compare and pool studies.”

Dr. Politi noted that there are ways to help patients now. “Most hospitals and health centers have staff who can talk to patients about their bills. Sometimes, a payment plan can be set up to space out payments,” she said. “Health care teams can try to consolidate care for patients on the same day to reduce parking expenses or time off for work or child care. Sometimes, changing to less expensive but effective generic medications is an option.”

The study authors received support from the National Cancer Institute, the United Nations Institute for Training and Research, the Global Surgery Foundation, the Harvard Global Health Institute, the Connors Center for Women’s Health and Gender Biology, the Center for Surgery and Public Health, and the National Endowment for Plastic Surgery. Dr. Ranganathan and Dr. Mekary report no disclosures. One coauthor reported a patent (BREAST-Q) and codevelopment of QPROMS, owned by Memorial Sloan Kettering Cancer Center. Another author reports salary support from Blue Cross Blue Shield of Michigan through the collaborative quality initiative known as Michigan Social Health Interventions to Eliminate Disparities. Dr. Politi has no disclosures.