Breast Cancer

Key clinical point: Denosumab improves bone-related outcomes in women with high-risk early-stage breast cancer.

Major finding: Denosumab was associated with longer time to first bone metastasis in patients younger than 50 years (hazard ratio [HR], 0.70; P = .018) and in premenopausal women (HR, 0.74; P = .038). Denosumab also delayed the risk for first fracture (HR, 0.76; P = .004) and first skeletal-related event (HR, 0.52; P = .001).

Study details: An exploratory analysis of randomized, placebo-controlled phase 3 D-CARE trial of 4,509 patients with stage II/III breast cancer randomly assigned to receive adjuvant/neoadjuvant chemotherapy with either denosumab or placebo.

Disclosures: This study was funded by Amgen Inc. Dr. R Coleman received lecture funding, steering committee fees, and travel expenses from various sources and reported stock ownership in Inbiomotion. Dr. Y. Zhou, Dr. D. Jandial, and Dr. B. Cadieux were employees of and/or shareholders in Amgen. The other authors have no competing interest.

Source: Coleman R et al. Adv Ther. 2021 Jun 29. doi: 10.1007/s12325-021-01812-9.

Key clinical point: Denosumab improves bone-related outcomes in women with high-risk early-stage breast cancer.

Major finding: Denosumab was associated with longer time to first bone metastasis in patients younger than 50 years (hazard ratio [HR], 0.70; P = .018) and in premenopausal women (HR, 0.74; P = .038). Denosumab also delayed the risk for first fracture (HR, 0.76; P = .004) and first skeletal-related event (HR, 0.52; P = .001).

Study details: An exploratory analysis of randomized, placebo-controlled phase 3 D-CARE trial of 4,509 patients with stage II/III breast cancer randomly assigned to receive adjuvant/neoadjuvant chemotherapy with either denosumab or placebo.

Disclosures: This study was funded by Amgen Inc. Dr. R Coleman received lecture funding, steering committee fees, and travel expenses from various sources and reported stock ownership in Inbiomotion. Dr. Y. Zhou, Dr. D. Jandial, and Dr. B. Cadieux were employees of and/or shareholders in Amgen. The other authors have no competing interest.

Source: Coleman R et al. Adv Ther. 2021 Jun 29. doi: 10.1007/s12325-021-01812-9.

Key clinical point: Denosumab improves bone-related outcomes in women with high-risk early-stage breast cancer.

Major finding: Denosumab was associated with longer time to first bone metastasis in patients younger than 50 years (hazard ratio [HR], 0.70; P = .018) and in premenopausal women (HR, 0.74; P = .038). Denosumab also delayed the risk for first fracture (HR, 0.76; P = .004) and first skeletal-related event (HR, 0.52; P = .001).

Study details: An exploratory analysis of randomized, placebo-controlled phase 3 D-CARE trial of 4,509 patients with stage II/III breast cancer randomly assigned to receive adjuvant/neoadjuvant chemotherapy with either denosumab or placebo.

Disclosures: This study was funded by Amgen Inc. Dr. R Coleman received lecture funding, steering committee fees, and travel expenses from various sources and reported stock ownership in Inbiomotion. Dr. Y. Zhou, Dr. D. Jandial, and Dr. B. Cadieux were employees of and/or shareholders in Amgen. The other authors have no competing interest.

Source: Coleman R et al. Adv Ther. 2021 Jun 29. doi: 10.1007/s12325-021-01812-9.

Key clinical point: The clinical benefit of ribociclib is maintained in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who required dose reduction to manage adverse events.

Major finding: Ribociclib dose reductions were reported in 45.8% of patients; most were attributed to adverse reactions. The median progression-free survival was 24.8, 24.9, and 29.6 months for patients who received 71% or less, 72%-96%, and 97%-100% ribociclib relative dose intensity, respectively. The clinical benefit ratio was 87.6%, 76.8%, and 73.6%, respectively.

Study details: A pooled analysis of MONALEESA-2, MONALEESA-3, and MONALEESA-7 trials evaluated the safety and impact of ribociclib dose reduction in 818 patients with HR-positive, HER2-negative advanced breast cancer.

Disclosures: The study was supported by Novartis Pharmaceuticals Corporation. The authors received grants, funding, and/or consulting/advisory/personal fees from various sources. Dr. JP Zarate, Dr. A Ridolfi, and Dr. KR Lorenc were employed by and owned stocks in Novartis.

Source: Burris HA et al. Br J Cancer. 2021 Jun 22. doi: 10.1038/s41416-021-01415-9.

Key clinical point: The clinical benefit of ribociclib is maintained in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who required dose reduction to manage adverse events.

Major finding: Ribociclib dose reductions were reported in 45.8% of patients; most were attributed to adverse reactions. The median progression-free survival was 24.8, 24.9, and 29.6 months for patients who received 71% or less, 72%-96%, and 97%-100% ribociclib relative dose intensity, respectively. The clinical benefit ratio was 87.6%, 76.8%, and 73.6%, respectively.

Study details: A pooled analysis of MONALEESA-2, MONALEESA-3, and MONALEESA-7 trials evaluated the safety and impact of ribociclib dose reduction in 818 patients with HR-positive, HER2-negative advanced breast cancer.

Disclosures: The study was supported by Novartis Pharmaceuticals Corporation. The authors received grants, funding, and/or consulting/advisory/personal fees from various sources. Dr. JP Zarate, Dr. A Ridolfi, and Dr. KR Lorenc were employed by and owned stocks in Novartis.

Source: Burris HA et al. Br J Cancer. 2021 Jun 22. doi: 10.1038/s41416-021-01415-9.

Key clinical point: The clinical benefit of ribociclib is maintained in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who required dose reduction to manage adverse events.

Major finding: Ribociclib dose reductions were reported in 45.8% of patients; most were attributed to adverse reactions. The median progression-free survival was 24.8, 24.9, and 29.6 months for patients who received 71% or less, 72%-96%, and 97%-100% ribociclib relative dose intensity, respectively. The clinical benefit ratio was 87.6%, 76.8%, and 73.6%, respectively.

Study details: A pooled analysis of MONALEESA-2, MONALEESA-3, and MONALEESA-7 trials evaluated the safety and impact of ribociclib dose reduction in 818 patients with HR-positive, HER2-negative advanced breast cancer.

Disclosures: The study was supported by Novartis Pharmaceuticals Corporation. The authors received grants, funding, and/or consulting/advisory/personal fees from various sources. Dr. JP Zarate, Dr. A Ridolfi, and Dr. KR Lorenc were employed by and owned stocks in Novartis.

Source: Burris HA et al. Br J Cancer. 2021 Jun 22. doi: 10.1038/s41416-021-01415-9.

Key clinical point: In patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, CT-P6, a trastuzumab biosimilar shows 3-year survival comparable with trastuzumab.

Major finding: Median disease-free survival (DFS), overall survival (OS), and progression-free survival (PFS) were not reached in either group. In the CT-P6 vs trastuzumab group, the 3-year DFS, PFS, and OS rates were 83% vs 83%, 81% vs 87%, and 93% vs 94%, respectively.

Study details: A randomized, double-blind, active-controlled, phase 3 equivalence trial of 549 patients with HER2‑positive early breast cancer who received neoadjuvant treatment with CT-P6 or trastuzumab with chemotherapy, followed by surgery. Patients were followed up for 3 years (n=528) after receiving adjuvant CT-P6 or trastuzumab.

Disclosures: The study was funded by Celltrion, Inc. The authors received grants and consulting/advisory fees from various sources. Dr. SJ Lee and Dr. S Kim were employees of and/or stockholders in Celltrion.

Source: Stebbing J et al. Breast Cancer Res Treat. 2021 Jun 20. doi: 10.1007/s10549-021-06240-5.

Key clinical point: In patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, CT-P6, a trastuzumab biosimilar shows 3-year survival comparable with trastuzumab.

Major finding: Median disease-free survival (DFS), overall survival (OS), and progression-free survival (PFS) were not reached in either group. In the CT-P6 vs trastuzumab group, the 3-year DFS, PFS, and OS rates were 83% vs 83%, 81% vs 87%, and 93% vs 94%, respectively.

Study details: A randomized, double-blind, active-controlled, phase 3 equivalence trial of 549 patients with HER2‑positive early breast cancer who received neoadjuvant treatment with CT-P6 or trastuzumab with chemotherapy, followed by surgery. Patients were followed up for 3 years (n=528) after receiving adjuvant CT-P6 or trastuzumab.

Disclosures: The study was funded by Celltrion, Inc. The authors received grants and consulting/advisory fees from various sources. Dr. SJ Lee and Dr. S Kim were employees of and/or stockholders in Celltrion.

Source: Stebbing J et al. Breast Cancer Res Treat. 2021 Jun 20. doi: 10.1007/s10549-021-06240-5.

Key clinical point: In patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer, CT-P6, a trastuzumab biosimilar shows 3-year survival comparable with trastuzumab.

Major finding: Median disease-free survival (DFS), overall survival (OS), and progression-free survival (PFS) were not reached in either group. In the CT-P6 vs trastuzumab group, the 3-year DFS, PFS, and OS rates were 83% vs 83%, 81% vs 87%, and 93% vs 94%, respectively.

Study details: A randomized, double-blind, active-controlled, phase 3 equivalence trial of 549 patients with HER2‑positive early breast cancer who received neoadjuvant treatment with CT-P6 or trastuzumab with chemotherapy, followed by surgery. Patients were followed up for 3 years (n=528) after receiving adjuvant CT-P6 or trastuzumab.

Disclosures: The study was funded by Celltrion, Inc. The authors received grants and consulting/advisory fees from various sources. Dr. SJ Lee and Dr. S Kim were employees of and/or stockholders in Celltrion.

Source: Stebbing J et al. Breast Cancer Res Treat. 2021 Jun 20. doi: 10.1007/s10549-021-06240-5.

Key clinical point: Bisphosphonate therapy for 5 vs 2 years in patients with high-risk early breast cancer yields no added survival benefit and leads to increased risk for adverse events.

Major finding: There were no significant differences in disease-free survival (hazard ratio [HR], 0.97; P = .81), overall survival (HR, 0.98; P = .90), and distant disease-free survival (HR, 0.87; P = .38) between 5- and 2-year bisphosphonate treatment groups. The rate of adverse events was 46.2% with 5-year therapy and 27.2% with 2-year treatment.

Study details: A randomized phase 3, open-label SUCCESS A trial of 2,987 patients with high-risk early breast cancer randomly assigned to receive bisphosphonate zoledronate for either 5 or 2 years.

Disclosures: The study was supported by AstraZeneca, Chugai, Menarini Silicon Biosystems (formerly Veridex), Lilly, Novartis, and Sanofi-Aventis. The authors received honoraria, personal fees, research support, consulting fees, and travel grants from various sources.

Source: Friedl TWP et al. JAMA Oncol. 2021 Jun 24. doi: 10.1001/jamaoncol.2021.1854.

Key clinical point: Bisphosphonate therapy for 5 vs 2 years in patients with high-risk early breast cancer yields no added survival benefit and leads to increased risk for adverse events.

Major finding: There were no significant differences in disease-free survival (hazard ratio [HR], 0.97; P = .81), overall survival (HR, 0.98; P = .90), and distant disease-free survival (HR, 0.87; P = .38) between 5- and 2-year bisphosphonate treatment groups. The rate of adverse events was 46.2% with 5-year therapy and 27.2% with 2-year treatment.

Study details: A randomized phase 3, open-label SUCCESS A trial of 2,987 patients with high-risk early breast cancer randomly assigned to receive bisphosphonate zoledronate for either 5 or 2 years.

Disclosures: The study was supported by AstraZeneca, Chugai, Menarini Silicon Biosystems (formerly Veridex), Lilly, Novartis, and Sanofi-Aventis. The authors received honoraria, personal fees, research support, consulting fees, and travel grants from various sources.

Source: Friedl TWP et al. JAMA Oncol. 2021 Jun 24. doi: 10.1001/jamaoncol.2021.1854.

Key clinical point: Bisphosphonate therapy for 5 vs 2 years in patients with high-risk early breast cancer yields no added survival benefit and leads to increased risk for adverse events.

Major finding: There were no significant differences in disease-free survival (hazard ratio [HR], 0.97; P = .81), overall survival (HR, 0.98; P = .90), and distant disease-free survival (HR, 0.87; P = .38) between 5- and 2-year bisphosphonate treatment groups. The rate of adverse events was 46.2% with 5-year therapy and 27.2% with 2-year treatment.

Study details: A randomized phase 3, open-label SUCCESS A trial of 2,987 patients with high-risk early breast cancer randomly assigned to receive bisphosphonate zoledronate for either 5 or 2 years.

Disclosures: The study was supported by AstraZeneca, Chugai, Menarini Silicon Biosystems (formerly Veridex), Lilly, Novartis, and Sanofi-Aventis. The authors received honoraria, personal fees, research support, consulting fees, and travel grants from various sources.

Source: Friedl TWP et al. JAMA Oncol. 2021 Jun 24. doi: 10.1001/jamaoncol.2021.1854.

Key clinical point: In patients with human epidermal growth factor receptor 2 (HER2)-positive locally recurrent or metastatic breast cancer, paclitaxel can be an alternative to docetaxel with first-line pertuzumab plus trastuzumab.

Major finding: The median follow-up was 68.7 months. The median progression-free survival was 19.4 (95% confidence interval [CI], 16.9-22.1) months in the docetaxel, 23.2 (95% CI,19.6-25.6) months in the paclitaxel, and 19.2 (95% CI, 11.7-37.1) months in the nab-paclitaxel group. Docetaxel was associated with higher rates of grade ≥3 neutropenia and febrile neutropenia.

Study details: A multicenter, open-label, single-arm phase 3b PERUSE study of 1,436 eligible patients with inoperable HER2-positive locally recurrent or metastatic breast cancer who received pertuzumab and trastuzumab with a taxane (docetaxel, paclitaxel, or nab-paclitaxel).

Disclosures: The study was supported by F. Hoffmann-La Roche Ltd, Basel, Switzerland. The authors reported receiving research funding, personal fees, grants, honoraria, advisory/speaker/consulting fees, and travel/accommodation/expenses from various sources. Some authors were employed by and/or owned stocks in pharmaceutical companies.

Source: Miles D et al. Ann Oncol. 2021 Jul 1. doi: 10.1016/j.annonc.2021.06.024.

Key clinical point: In patients with human epidermal growth factor receptor 2 (HER2)-positive locally recurrent or metastatic breast cancer, paclitaxel can be an alternative to docetaxel with first-line pertuzumab plus trastuzumab.

Major finding: The median follow-up was 68.7 months. The median progression-free survival was 19.4 (95% confidence interval [CI], 16.9-22.1) months in the docetaxel, 23.2 (95% CI,19.6-25.6) months in the paclitaxel, and 19.2 (95% CI, 11.7-37.1) months in the nab-paclitaxel group. Docetaxel was associated with higher rates of grade ≥3 neutropenia and febrile neutropenia.

Study details: A multicenter, open-label, single-arm phase 3b PERUSE study of 1,436 eligible patients with inoperable HER2-positive locally recurrent or metastatic breast cancer who received pertuzumab and trastuzumab with a taxane (docetaxel, paclitaxel, or nab-paclitaxel).

Disclosures: The study was supported by F. Hoffmann-La Roche Ltd, Basel, Switzerland. The authors reported receiving research funding, personal fees, grants, honoraria, advisory/speaker/consulting fees, and travel/accommodation/expenses from various sources. Some authors were employed by and/or owned stocks in pharmaceutical companies.

Source: Miles D et al. Ann Oncol. 2021 Jul 1. doi: 10.1016/j.annonc.2021.06.024.

Key clinical point: In patients with human epidermal growth factor receptor 2 (HER2)-positive locally recurrent or metastatic breast cancer, paclitaxel can be an alternative to docetaxel with first-line pertuzumab plus trastuzumab.

Major finding: The median follow-up was 68.7 months. The median progression-free survival was 19.4 (95% confidence interval [CI], 16.9-22.1) months in the docetaxel, 23.2 (95% CI,19.6-25.6) months in the paclitaxel, and 19.2 (95% CI, 11.7-37.1) months in the nab-paclitaxel group. Docetaxel was associated with higher rates of grade ≥3 neutropenia and febrile neutropenia.

Study details: A multicenter, open-label, single-arm phase 3b PERUSE study of 1,436 eligible patients with inoperable HER2-positive locally recurrent or metastatic breast cancer who received pertuzumab and trastuzumab with a taxane (docetaxel, paclitaxel, or nab-paclitaxel).

Disclosures: The study was supported by F. Hoffmann-La Roche Ltd, Basel, Switzerland. The authors reported receiving research funding, personal fees, grants, honoraria, advisory/speaker/consulting fees, and travel/accommodation/expenses from various sources. Some authors were employed by and/or owned stocks in pharmaceutical companies.

Source: Miles D et al. Ann Oncol. 2021 Jul 1. doi: 10.1016/j.annonc.2021.06.024.

Key clinical point: Atezolizumab plus nab-paclitaxel shows no overall survival (OS) advantage in patients with advanced/metastatic triple-negative breast cancer (TNBC) overall, but improves OS in in a patient subgroup positive for programmed death-ligand 1 (PD-L1) expression in tumor-infiltrating immune cells.

Major finding: There was no difference in OS in the intent-to-treat population (P = .077). An exploratory analysis in the PD-L1 immune cell-positive population showed OS improvement with atezolizumab plus nab-paclitaxel (stratified hazard ratio, 0.67; 95% confidence interval, 0.53-0.86).

Study details: A randomized, double-blind, placebo-controlled phase 3 IMpassion130 trial of 902 patients with advanced/metastatic TNBC who received atezolizumab plus nab-paclitaxel (n=451) or placebo plus nab-paclitaxel (n=451).

Disclosures: This study was sponsored by F. Hoffmann-La Roche Ltd./Genentech, Inc. The authors received honoraria, travel support, research funding, consulting/advisory/steering committee fees, and grants from various sources. Some of the authors were employed by and/or owned stocks in Genentech/Roche.

Source: Emens LA et al. Ann Oncol. 2021 Jul 1. doi: 10.1016/j.annonc.2021.05.355.

Key clinical point: Atezolizumab plus nab-paclitaxel shows no overall survival (OS) advantage in patients with advanced/metastatic triple-negative breast cancer (TNBC) overall, but improves OS in in a patient subgroup positive for programmed death-ligand 1 (PD-L1) expression in tumor-infiltrating immune cells.

Major finding: There was no difference in OS in the intent-to-treat population (P = .077). An exploratory analysis in the PD-L1 immune cell-positive population showed OS improvement with atezolizumab plus nab-paclitaxel (stratified hazard ratio, 0.67; 95% confidence interval, 0.53-0.86).

Study details: A randomized, double-blind, placebo-controlled phase 3 IMpassion130 trial of 902 patients with advanced/metastatic TNBC who received atezolizumab plus nab-paclitaxel (n=451) or placebo plus nab-paclitaxel (n=451).

Disclosures: This study was sponsored by F. Hoffmann-La Roche Ltd./Genentech, Inc. The authors received honoraria, travel support, research funding, consulting/advisory/steering committee fees, and grants from various sources. Some of the authors were employed by and/or owned stocks in Genentech/Roche.

Source: Emens LA et al. Ann Oncol. 2021 Jul 1. doi: 10.1016/j.annonc.2021.05.355.

Key clinical point: Atezolizumab plus nab-paclitaxel shows no overall survival (OS) advantage in patients with advanced/metastatic triple-negative breast cancer (TNBC) overall, but improves OS in in a patient subgroup positive for programmed death-ligand 1 (PD-L1) expression in tumor-infiltrating immune cells.

Major finding: There was no difference in OS in the intent-to-treat population (P = .077). An exploratory analysis in the PD-L1 immune cell-positive population showed OS improvement with atezolizumab plus nab-paclitaxel (stratified hazard ratio, 0.67; 95% confidence interval, 0.53-0.86).

Study details: A randomized, double-blind, placebo-controlled phase 3 IMpassion130 trial of 902 patients with advanced/metastatic TNBC who received atezolizumab plus nab-paclitaxel (n=451) or placebo plus nab-paclitaxel (n=451).

Disclosures: This study was sponsored by F. Hoffmann-La Roche Ltd./Genentech, Inc. The authors received honoraria, travel support, research funding, consulting/advisory/steering committee fees, and grants from various sources. Some of the authors were employed by and/or owned stocks in Genentech/Roche.

Source: Emens LA et al. Ann Oncol. 2021 Jul 1. doi: 10.1016/j.annonc.2021.05.355.

Key clinical point: Atezolizumab in combination with paclitaxel does not improve survival in patients with unresectable locally advanced/metastatic triple-negative breast cancer (TNBC) vs paclitaxel plus placebo.

Major finding: The median follow-up was 14.2 months in the atezolizumab group and 14.5 months in the placebo group. Atezolizumab plus paclitaxel did not improve median overall survival vs paclitaxel plus placebo (hazard ratio, 1.11; 95% confidence interval, 0.76-1.64). Compared with placebo plus paclitaxel, atezolizumab plus paclitaxel was associated with a higher incidence of serious (25% vs 18%) and grade 3/4 adverse events (53% vs 46%).

Study details: A global randomized, double-blind, placebo-controlled phase 3 IMpassion131 trial of 651 patients with advanced/metastatic TNBC who were randomly assigned to atezolizumab plus paclitaxel or placebo plus paclitaxel.

Disclosures: The study was supported by F. Hoffmann-La Roche Ltd. The authors received honoraria, research grants, speaker/advisory/consulting fees, personal fees, and travel/accommodation/expenses from various sources. Some authors were employed by and/or owned stocks in pharmaceutical companies.

Source: Miles D et al. Ann Oncol. 2021 Jul 1. doi: 10.1016/j.annonc.2021.05.801.

Key clinical point: Atezolizumab in combination with paclitaxel does not improve survival in patients with unresectable locally advanced/metastatic triple-negative breast cancer (TNBC) vs paclitaxel plus placebo.

Major finding: The median follow-up was 14.2 months in the atezolizumab group and 14.5 months in the placebo group. Atezolizumab plus paclitaxel did not improve median overall survival vs paclitaxel plus placebo (hazard ratio, 1.11; 95% confidence interval, 0.76-1.64). Compared with placebo plus paclitaxel, atezolizumab plus paclitaxel was associated with a higher incidence of serious (25% vs 18%) and grade 3/4 adverse events (53% vs 46%).

Study details: A global randomized, double-blind, placebo-controlled phase 3 IMpassion131 trial of 651 patients with advanced/metastatic TNBC who were randomly assigned to atezolizumab plus paclitaxel or placebo plus paclitaxel.

Disclosures: The study was supported by F. Hoffmann-La Roche Ltd. The authors received honoraria, research grants, speaker/advisory/consulting fees, personal fees, and travel/accommodation/expenses from various sources. Some authors were employed by and/or owned stocks in pharmaceutical companies.

Source: Miles D et al. Ann Oncol. 2021 Jul 1. doi: 10.1016/j.annonc.2021.05.801.

Key clinical point: Atezolizumab in combination with paclitaxel does not improve survival in patients with unresectable locally advanced/metastatic triple-negative breast cancer (TNBC) vs paclitaxel plus placebo.

Major finding: The median follow-up was 14.2 months in the atezolizumab group and 14.5 months in the placebo group. Atezolizumab plus paclitaxel did not improve median overall survival vs paclitaxel plus placebo (hazard ratio, 1.11; 95% confidence interval, 0.76-1.64). Compared with placebo plus paclitaxel, atezolizumab plus paclitaxel was associated with a higher incidence of serious (25% vs 18%) and grade 3/4 adverse events (53% vs 46%).

Study details: A global randomized, double-blind, placebo-controlled phase 3 IMpassion131 trial of 651 patients with advanced/metastatic TNBC who were randomly assigned to atezolizumab plus paclitaxel or placebo plus paclitaxel.

Disclosures: The study was supported by F. Hoffmann-La Roche Ltd. The authors received honoraria, research grants, speaker/advisory/consulting fees, personal fees, and travel/accommodation/expenses from various sources. Some authors were employed by and/or owned stocks in pharmaceutical companies.

Source: Miles D et al. Ann Oncol. 2021 Jul 1. doi: 10.1016/j.annonc.2021.05.801.

Clinical trials underway across the United States are exploring the use of robotic surgical devices for nipple-sparing mastectomy, but are either not collecting cancer outcomes or not doing so as a primary measure – despite a stiff warning from the Food and Drug Administration that those outcomes are important.

The FDA warning was issued in February 2019 to both the public and physicians. The FDA cautioned that the safety and effectiveness of robotic surgical devices for mastectomy “have not been established” and robots are not approved for the prevention or treatment of breast cancer.

The agency also noted that “diminished long-term survival” was associated with robotic surgery in another women’s cancer, that of hysterectomy for cervical cancer.

The FDA also made a surprising statement. The agency typically approves the robot for surgical use based on 30-day complication rates (compared with standards of care). But it said that going forward it “anticipates” that any evaluation of new use of robots in cancer “would be supported” by cancer outcomes such as progression-free survival and overall survival, which require much longer follow-up.

In short, the FDA hinted that it would change how it regulated medical devices, or at least robots used in women’s cancers. “The FDA takes women’s health very seriously,” said the organization.

Fast forward to 2021, and there are several prospective clinical trials of robot-assisted nipple-sparing mastectomy underway in the United States, including a five-center study sponsored by Intuitive Surgical, the maker of da Vinci robots, the dominant machine on the market. There are also single-center studies at Ohio State and University of Texas Southwestern Medical Center.

However, in each case, the study design either excludes cancer outcomes or does not primarily focus on those measures.

Instead, the primary outcomes are relatively short term and include safety and efficacy measures such as en bloc (in one piece) removal of the breast tissue, conversions to open mastectomy, and the incidence of adverse events during surgery and up to 6 weeks after surgery.

Importantly, none of the studies is a randomized trial; all have single arms.

That’s not what is needed, says breast surgeon Julie A. Margenthaler, MD of Washington University in St. Louis.

“I firmly believe that robotic-assisted mastectomy should only be considered in the context of a well-designed, randomized trial evaluating patient selection, patient safety, surgical complications, and oncologic outcomes with a concomitant cost analysis,” Dr. Margenthaler wrote in an essay published last year in JAMA Surgery.

As with the FDA warning, she cites worse survival with commonly used minimally invasive radical hysterectomy for cervical cancer, saying it “is a stark reminder that the marketing of robotic surgery has its roots in cosmesis and convenience rather than oncologic outcomes.”

In addition, robotic surgery is prohibitively expensive, said Dr. Margenthaler. In fact, cost is her “main criticism regarding robotic-assisted mastectomy.” It costs an additional $6,000 for robot use per procedure, according to a study conducted at a center in Taiwan. “I simply cannot be convinced that this will ever achieve cost-effective or even cost-neutral status,” Dr. Margenthaler wrote.
 

Not looking at the right outcomes

“They’re not looking at the right outcomes,” said Hooman Noorchashm, MD, PhD, about the current trials in the United States. He is a former surgeon and faculty member at the University of Pennsylvania in Philadelphia, and is now a patient advocate after his wife, Amy Reed, MD, died of uterine cancer in 2017 following a laparoscopic hysterectomy performed with a power morcellator that resulted in the upstaging of an undetected gynecologic cancer.

“You have to look at oncologic outcomes and do randomized, noninferiority trials to demonstrate that those cancer outcomes are at least equivalent to standard of care,” he said in an interview.

The current U.S. trials are “totally inappropriate,” he said.

Are randomized trials forthcoming after this initial set of single-arm trials? This news organization reached out to Intuitive Surgical, maker of the market leader da Vinci robotic surgical equipment to find out.  

“Any plans for use of da Vinci Xi surgical system in nipple-sparing mastectomy will be based on these [single-arm] study results as well as other data and evidence,” said a company spokesperson, who did not confirm use of a randomized trial.

What about the FDA? Will the agency change its current approach to approving robots in surgeries for women’s cancers and require – not just anticipate – cancer-related outcomes data? At press time, the FDA did not respond to a request for comment.  

Not having a randomized trial with cancer outcomes in any eventual FDA review opens the door for robotic mastectomy to be cleared for use in some mastectomies with short-term, nononcologic data, said Dr. Noorchashm.
 

Safety concerns with robotic mastectomy

Proponents of robot-assisted nipple-sparing mastectomy, which is coupled with reconstruction to preserve the shape of both the breast and nipple-areola area, suggest that improved patient cosmesis is a significant advantage with the high-tech intervention, said Dr. Margenthaler.

That’s because most robotic mastectomies performed to date (almost exclusively in Europe and Asia) have employed a 3- to 5-cm vertical incision located behind the lateral breast fold, allowing the scar to be hidden under the patient’s arm.

But therein also lies a safety concern, she asserted.

The “oncologic integrity” of the specimen on extraction is in question in some cases, she wrote, because of “such a small opening.”

Dr. Noorchashm agreed: “It all comes down to trying to get a large specimen out of a small incision.”

Traditional open mastectomy optimally yields the en bloc removal of a tumor – in one whole piece – to avoid fragmenting the cancerous tissue and possibly leaving residual disease behind. These undesirable events are associated with a higher risk for recurrence and treatment failure, he explained.

Thus, there is a need for a randomized trial with longer-term oncologic outcomes that compares the new approach with traditional open mastectomy, argued both Dr. Margenthaler and Dr. Noorchashm.
 

In defense of single-arm trials

“Oncologic safety is what we are concerned about and what we would like to study,” said Ko Un (Clara) Park, MD, a breast surgeon at The Ohio State University in Columbus.

Dr. Park is leading a single-center, single-arm pilot study of robotic nipple-sparing mastectomy enrolling up to 20 women with early-stage breast cancer or inherited genetic risk factors (but no cancer diagnosis). The trial, sponsored by a Pelotonia Idea Grant and Ohio State, recently enrolled its first patient.

The study’s primary outcomes include the feasibility of removal of the breast tissue en bloc; however, none of the outcomes are classic oncologic metrics such as progression-free survival.

The en bloc removal outcome is in direct response to the FDA’s concerns about minimally invasive cancer surgeries in women, Dr. Park said in an interview. The pilot trial has an investigational device exemption (IDE) granted by the FDA.

“The reason why we can’t just open a randomized controlled study (of robot versus open) and measure oncologic outcomes like recurrence-free survival is because, before we get to that point, we have to make sure” basic safety issues are addressed and established, she explained.

But Dr. Noorchashm said that argument is missing the larger, more important point: “They are still doing an oncologic procedure – you are still obliged to do noninferiority [randomized] testing with respect to cancer outcomes.”

Dr. Park sounded a different note: “We are doing it as safely as we can do it.”
 

Prophylactic use is also a cancer surgery

Intuitive’s five-center trial does not include en bloc removal of the breast gland as a primary outcome. Instead, the two primary outcomes are conversions to open mastectomy (efficacy measure) and the incidence of adverse events during surgery to 42 days after surgery (safety measure).

The company’s trial does not include any women with breast cancer, but is limited to women at increased risk for breast cancer and seeking prophylactic nipple-sparing mastectomy surgery.

Enrollment in the 145-patient single-arm trial began in the last few months and has a primary completion date of December 2022. It also has an IDE from the FDA.

“I do think that things like this need to be done with caution,” said Katherine Kopkash, MD, an investigator in the Intuitive trial and a breast surgeon at NorthShore University HealthSystem in Evanston, Ill., referring to the trial’s FDA exemption.  

Dr. Kopkash said in an interview that the researchers in the multisite, single-arm Intuitive trial will also track oncologic outcomes, but the trial description at clinicaltrials.gov does not indicate that.

Both Dr. Kopkash and Dr. Park cited the high-profile missteps that took place in 2018 at Monmouth County Medical Center in Long Branch, N.J., during what was described as the first-ever use of robotic nipple-sparing mastectomy for invasive cancer in the United States, as reported by Medscape Medical News. However, neither the center or surgeon, Stephen Chagares, MD, requested or received an IDE from the FDA, and use of robotic mastectomy was halted after two cases.

It’s conceivable that Intuitive will seek out FDA clearance for use of its da Vinci system in robotic nipple-sparing mastectomy with data in a prophylactic setting and then expand the pool of patients, argued Dr. Noorchashm.

“Even if you introduce a new technology ... for a narrow subset of patients, the application of it eventually occurs on a ‘sliding scale,’ ” he said.

The former surgeon gave an example: The first device used in gastric bypass surgery was cleared for use in 2001 by the FDA for adults who were “severely morbidly obese.” But by the late 2000s, the operation was also being performed on people with lower body mass indexes who hadn’t exhausted traditional weight loss procedures. “It was very lucrative,” Dr. Noorchashm said about the surgery.
 

Surgeons only get one body

Intuitive has been hugely successful in developing and marketing its da Vinci system around the world for general and oncologic surgeries, with more than 1 million surgeries in 2018, a greater than sevenfold increase in 10 years, according to the authors of a new essay published in the June issue of the Annals of Surgery. The authors include breast surgeon Rosa F. Hwang, MD, of MD Anderson Cancer Center in Houston, who is also an investigator for the Intuitive trial.

However, robotic mastectomy is still a new surgery – only about 150 patients have been treated in the world, mostly in Italy, France, Taiwan, and Korea, the authors noted.

Despite such small numbers, “there’s a lot of interest in bringing this to the United States,” said Dr. Park.

One of the arguments in favor of robotic mastectomy for nipple-sparing procedures has nothing to do with patients. Instead, it is improved ergonomics – the robot makes a tough surgery easier on the surgeon.

Even stalwart robot critic Dr. Margenthaler conceded that this was possibly a winning feature.

“Nipple-sparing mastectomy is a very physically demanding procedure for the surgeon, resulting in higher rates of neck and back pain and fatigue compared with a standard skin-sparing approach,” she noted. She suggested, however, that practitioners of traditional mastectomy ought to first experiment with changes to patient positioning and incision placement to alleviate stress before looking to the robot for change.

When this news organization interviewed NorthShore University’s Dr. Kopkash, she had conducted four nipple-sparing mastectomies in the previous week. “It’s a difficult procedure on our bodies. I just turned 40 and I’m considered young for a surgeon. We get one body for our career and we have to figure out ways to make it work and protect it.”

Intuitive Surgical is funding the five-center clinical trial of robot-assisted nipple-sparing mastectomy, and UT Southwestern is funding its own trial. The Ohio State trial is funded by the university and a Pelotonia Idea Grant. Dr. Noorchashm and Dr. Margenthaler have no relevant financial disclosures.

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

Clinical trials underway across the United States are exploring the use of robotic surgical devices for nipple-sparing mastectomy, but are either not collecting cancer outcomes or not doing so as a primary measure – despite a stiff warning from the Food and Drug Administration that those outcomes are important.

The FDA warning was issued in February 2019 to both the public and physicians. The FDA cautioned that the safety and effectiveness of robotic surgical devices for mastectomy “have not been established” and robots are not approved for the prevention or treatment of breast cancer.

The agency also noted that “diminished long-term survival” was associated with robotic surgery in another women’s cancer, that of hysterectomy for cervical cancer.

The FDA also made a surprising statement. The agency typically approves the robot for surgical use based on 30-day complication rates (compared with standards of care). But it said that going forward it “anticipates” that any evaluation of new use of robots in cancer “would be supported” by cancer outcomes such as progression-free survival and overall survival, which require much longer follow-up.

In short, the FDA hinted that it would change how it regulated medical devices, or at least robots used in women’s cancers. “The FDA takes women’s health very seriously,” said the organization.

Fast forward to 2021, and there are several prospective clinical trials of robot-assisted nipple-sparing mastectomy underway in the United States, including a five-center study sponsored by Intuitive Surgical, the maker of da Vinci robots, the dominant machine on the market. There are also single-center studies at Ohio State and University of Texas Southwestern Medical Center.

However, in each case, the study design either excludes cancer outcomes or does not primarily focus on those measures.

Instead, the primary outcomes are relatively short term and include safety and efficacy measures such as en bloc (in one piece) removal of the breast tissue, conversions to open mastectomy, and the incidence of adverse events during surgery and up to 6 weeks after surgery.

Importantly, none of the studies is a randomized trial; all have single arms.

That’s not what is needed, says breast surgeon Julie A. Margenthaler, MD of Washington University in St. Louis.

“I firmly believe that robotic-assisted mastectomy should only be considered in the context of a well-designed, randomized trial evaluating patient selection, patient safety, surgical complications, and oncologic outcomes with a concomitant cost analysis,” Dr. Margenthaler wrote in an essay published last year in JAMA Surgery.

As with the FDA warning, she cites worse survival with commonly used minimally invasive radical hysterectomy for cervical cancer, saying it “is a stark reminder that the marketing of robotic surgery has its roots in cosmesis and convenience rather than oncologic outcomes.”

In addition, robotic surgery is prohibitively expensive, said Dr. Margenthaler. In fact, cost is her “main criticism regarding robotic-assisted mastectomy.” It costs an additional $6,000 for robot use per procedure, according to a study conducted at a center in Taiwan. “I simply cannot be convinced that this will ever achieve cost-effective or even cost-neutral status,” Dr. Margenthaler wrote.
 

Not looking at the right outcomes

“They’re not looking at the right outcomes,” said Hooman Noorchashm, MD, PhD, about the current trials in the United States. He is a former surgeon and faculty member at the University of Pennsylvania in Philadelphia, and is now a patient advocate after his wife, Amy Reed, MD, died of uterine cancer in 2017 following a laparoscopic hysterectomy performed with a power morcellator that resulted in the upstaging of an undetected gynecologic cancer.

“You have to look at oncologic outcomes and do randomized, noninferiority trials to demonstrate that those cancer outcomes are at least equivalent to standard of care,” he said in an interview.

The current U.S. trials are “totally inappropriate,” he said.

Are randomized trials forthcoming after this initial set of single-arm trials? This news organization reached out to Intuitive Surgical, maker of the market leader da Vinci robotic surgical equipment to find out.  

“Any plans for use of da Vinci Xi surgical system in nipple-sparing mastectomy will be based on these [single-arm] study results as well as other data and evidence,” said a company spokesperson, who did not confirm use of a randomized trial.

What about the FDA? Will the agency change its current approach to approving robots in surgeries for women’s cancers and require – not just anticipate – cancer-related outcomes data? At press time, the FDA did not respond to a request for comment.  

Not having a randomized trial with cancer outcomes in any eventual FDA review opens the door for robotic mastectomy to be cleared for use in some mastectomies with short-term, nononcologic data, said Dr. Noorchashm.
 

Safety concerns with robotic mastectomy

Proponents of robot-assisted nipple-sparing mastectomy, which is coupled with reconstruction to preserve the shape of both the breast and nipple-areola area, suggest that improved patient cosmesis is a significant advantage with the high-tech intervention, said Dr. Margenthaler.

That’s because most robotic mastectomies performed to date (almost exclusively in Europe and Asia) have employed a 3- to 5-cm vertical incision located behind the lateral breast fold, allowing the scar to be hidden under the patient’s arm.

But therein also lies a safety concern, she asserted.

The “oncologic integrity” of the specimen on extraction is in question in some cases, she wrote, because of “such a small opening.”

Dr. Noorchashm agreed: “It all comes down to trying to get a large specimen out of a small incision.”

Traditional open mastectomy optimally yields the en bloc removal of a tumor – in one whole piece – to avoid fragmenting the cancerous tissue and possibly leaving residual disease behind. These undesirable events are associated with a higher risk for recurrence and treatment failure, he explained.

Thus, there is a need for a randomized trial with longer-term oncologic outcomes that compares the new approach with traditional open mastectomy, argued both Dr. Margenthaler and Dr. Noorchashm.
 

In defense of single-arm trials

“Oncologic safety is what we are concerned about and what we would like to study,” said Ko Un (Clara) Park, MD, a breast surgeon at The Ohio State University in Columbus.

Dr. Park is leading a single-center, single-arm pilot study of robotic nipple-sparing mastectomy enrolling up to 20 women with early-stage breast cancer or inherited genetic risk factors (but no cancer diagnosis). The trial, sponsored by a Pelotonia Idea Grant and Ohio State, recently enrolled its first patient.

The study’s primary outcomes include the feasibility of removal of the breast tissue en bloc; however, none of the outcomes are classic oncologic metrics such as progression-free survival.

The en bloc removal outcome is in direct response to the FDA’s concerns about minimally invasive cancer surgeries in women, Dr. Park said in an interview. The pilot trial has an investigational device exemption (IDE) granted by the FDA.

“The reason why we can’t just open a randomized controlled study (of robot versus open) and measure oncologic outcomes like recurrence-free survival is because, before we get to that point, we have to make sure” basic safety issues are addressed and established, she explained.

But Dr. Noorchashm said that argument is missing the larger, more important point: “They are still doing an oncologic procedure – you are still obliged to do noninferiority [randomized] testing with respect to cancer outcomes.”

Dr. Park sounded a different note: “We are doing it as safely as we can do it.”
 

Prophylactic use is also a cancer surgery

Intuitive’s five-center trial does not include en bloc removal of the breast gland as a primary outcome. Instead, the two primary outcomes are conversions to open mastectomy (efficacy measure) and the incidence of adverse events during surgery to 42 days after surgery (safety measure).

The company’s trial does not include any women with breast cancer, but is limited to women at increased risk for breast cancer and seeking prophylactic nipple-sparing mastectomy surgery.

Enrollment in the 145-patient single-arm trial began in the last few months and has a primary completion date of December 2022. It also has an IDE from the FDA.

“I do think that things like this need to be done with caution,” said Katherine Kopkash, MD, an investigator in the Intuitive trial and a breast surgeon at NorthShore University HealthSystem in Evanston, Ill., referring to the trial’s FDA exemption.  

Dr. Kopkash said in an interview that the researchers in the multisite, single-arm Intuitive trial will also track oncologic outcomes, but the trial description at clinicaltrials.gov does not indicate that.

Both Dr. Kopkash and Dr. Park cited the high-profile missteps that took place in 2018 at Monmouth County Medical Center in Long Branch, N.J., during what was described as the first-ever use of robotic nipple-sparing mastectomy for invasive cancer in the United States, as reported by Medscape Medical News. However, neither the center or surgeon, Stephen Chagares, MD, requested or received an IDE from the FDA, and use of robotic mastectomy was halted after two cases.

It’s conceivable that Intuitive will seek out FDA clearance for use of its da Vinci system in robotic nipple-sparing mastectomy with data in a prophylactic setting and then expand the pool of patients, argued Dr. Noorchashm.

“Even if you introduce a new technology ... for a narrow subset of patients, the application of it eventually occurs on a ‘sliding scale,’ ” he said.

The former surgeon gave an example: The first device used in gastric bypass surgery was cleared for use in 2001 by the FDA for adults who were “severely morbidly obese.” But by the late 2000s, the operation was also being performed on people with lower body mass indexes who hadn’t exhausted traditional weight loss procedures. “It was very lucrative,” Dr. Noorchashm said about the surgery.
 

Surgeons only get one body

Intuitive has been hugely successful in developing and marketing its da Vinci system around the world for general and oncologic surgeries, with more than 1 million surgeries in 2018, a greater than sevenfold increase in 10 years, according to the authors of a new essay published in the June issue of the Annals of Surgery. The authors include breast surgeon Rosa F. Hwang, MD, of MD Anderson Cancer Center in Houston, who is also an investigator for the Intuitive trial.

However, robotic mastectomy is still a new surgery – only about 150 patients have been treated in the world, mostly in Italy, France, Taiwan, and Korea, the authors noted.

Despite such small numbers, “there’s a lot of interest in bringing this to the United States,” said Dr. Park.

One of the arguments in favor of robotic mastectomy for nipple-sparing procedures has nothing to do with patients. Instead, it is improved ergonomics – the robot makes a tough surgery easier on the surgeon.

Even stalwart robot critic Dr. Margenthaler conceded that this was possibly a winning feature.

“Nipple-sparing mastectomy is a very physically demanding procedure for the surgeon, resulting in higher rates of neck and back pain and fatigue compared with a standard skin-sparing approach,” she noted. She suggested, however, that practitioners of traditional mastectomy ought to first experiment with changes to patient positioning and incision placement to alleviate stress before looking to the robot for change.

When this news organization interviewed NorthShore University’s Dr. Kopkash, she had conducted four nipple-sparing mastectomies in the previous week. “It’s a difficult procedure on our bodies. I just turned 40 and I’m considered young for a surgeon. We get one body for our career and we have to figure out ways to make it work and protect it.”

Intuitive Surgical is funding the five-center clinical trial of robot-assisted nipple-sparing mastectomy, and UT Southwestern is funding its own trial. The Ohio State trial is funded by the university and a Pelotonia Idea Grant. Dr. Noorchashm and Dr. Margenthaler have no relevant financial disclosures.

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

Clinical trials underway across the United States are exploring the use of robotic surgical devices for nipple-sparing mastectomy, but are either not collecting cancer outcomes or not doing so as a primary measure – despite a stiff warning from the Food and Drug Administration that those outcomes are important.

The FDA warning was issued in February 2019 to both the public and physicians. The FDA cautioned that the safety and effectiveness of robotic surgical devices for mastectomy “have not been established” and robots are not approved for the prevention or treatment of breast cancer.

The agency also noted that “diminished long-term survival” was associated with robotic surgery in another women’s cancer, that of hysterectomy for cervical cancer.

The FDA also made a surprising statement. The agency typically approves the robot for surgical use based on 30-day complication rates (compared with standards of care). But it said that going forward it “anticipates” that any evaluation of new use of robots in cancer “would be supported” by cancer outcomes such as progression-free survival and overall survival, which require much longer follow-up.

In short, the FDA hinted that it would change how it regulated medical devices, or at least robots used in women’s cancers. “The FDA takes women’s health very seriously,” said the organization.

Fast forward to 2021, and there are several prospective clinical trials of robot-assisted nipple-sparing mastectomy underway in the United States, including a five-center study sponsored by Intuitive Surgical, the maker of da Vinci robots, the dominant machine on the market. There are also single-center studies at Ohio State and University of Texas Southwestern Medical Center.

However, in each case, the study design either excludes cancer outcomes or does not primarily focus on those measures.

Instead, the primary outcomes are relatively short term and include safety and efficacy measures such as en bloc (in one piece) removal of the breast tissue, conversions to open mastectomy, and the incidence of adverse events during surgery and up to 6 weeks after surgery.

Importantly, none of the studies is a randomized trial; all have single arms.

That’s not what is needed, says breast surgeon Julie A. Margenthaler, MD of Washington University in St. Louis.

“I firmly believe that robotic-assisted mastectomy should only be considered in the context of a well-designed, randomized trial evaluating patient selection, patient safety, surgical complications, and oncologic outcomes with a concomitant cost analysis,” Dr. Margenthaler wrote in an essay published last year in JAMA Surgery.

As with the FDA warning, she cites worse survival with commonly used minimally invasive radical hysterectomy for cervical cancer, saying it “is a stark reminder that the marketing of robotic surgery has its roots in cosmesis and convenience rather than oncologic outcomes.”

In addition, robotic surgery is prohibitively expensive, said Dr. Margenthaler. In fact, cost is her “main criticism regarding robotic-assisted mastectomy.” It costs an additional $6,000 for robot use per procedure, according to a study conducted at a center in Taiwan. “I simply cannot be convinced that this will ever achieve cost-effective or even cost-neutral status,” Dr. Margenthaler wrote.
 

Not looking at the right outcomes

“They’re not looking at the right outcomes,” said Hooman Noorchashm, MD, PhD, about the current trials in the United States. He is a former surgeon and faculty member at the University of Pennsylvania in Philadelphia, and is now a patient advocate after his wife, Amy Reed, MD, died of uterine cancer in 2017 following a laparoscopic hysterectomy performed with a power morcellator that resulted in the upstaging of an undetected gynecologic cancer.

“You have to look at oncologic outcomes and do randomized, noninferiority trials to demonstrate that those cancer outcomes are at least equivalent to standard of care,” he said in an interview.

The current U.S. trials are “totally inappropriate,” he said.

Are randomized trials forthcoming after this initial set of single-arm trials? This news organization reached out to Intuitive Surgical, maker of the market leader da Vinci robotic surgical equipment to find out.  

“Any plans for use of da Vinci Xi surgical system in nipple-sparing mastectomy will be based on these [single-arm] study results as well as other data and evidence,” said a company spokesperson, who did not confirm use of a randomized trial.

What about the FDA? Will the agency change its current approach to approving robots in surgeries for women’s cancers and require – not just anticipate – cancer-related outcomes data? At press time, the FDA did not respond to a request for comment.  

Not having a randomized trial with cancer outcomes in any eventual FDA review opens the door for robotic mastectomy to be cleared for use in some mastectomies with short-term, nononcologic data, said Dr. Noorchashm.
 

Safety concerns with robotic mastectomy

Proponents of robot-assisted nipple-sparing mastectomy, which is coupled with reconstruction to preserve the shape of both the breast and nipple-areola area, suggest that improved patient cosmesis is a significant advantage with the high-tech intervention, said Dr. Margenthaler.

That’s because most robotic mastectomies performed to date (almost exclusively in Europe and Asia) have employed a 3- to 5-cm vertical incision located behind the lateral breast fold, allowing the scar to be hidden under the patient’s arm.

But therein also lies a safety concern, she asserted.

The “oncologic integrity” of the specimen on extraction is in question in some cases, she wrote, because of “such a small opening.”

Dr. Noorchashm agreed: “It all comes down to trying to get a large specimen out of a small incision.”

Traditional open mastectomy optimally yields the en bloc removal of a tumor – in one whole piece – to avoid fragmenting the cancerous tissue and possibly leaving residual disease behind. These undesirable events are associated with a higher risk for recurrence and treatment failure, he explained.

Thus, there is a need for a randomized trial with longer-term oncologic outcomes that compares the new approach with traditional open mastectomy, argued both Dr. Margenthaler and Dr. Noorchashm.
 

In defense of single-arm trials

“Oncologic safety is what we are concerned about and what we would like to study,” said Ko Un (Clara) Park, MD, a breast surgeon at The Ohio State University in Columbus.

Dr. Park is leading a single-center, single-arm pilot study of robotic nipple-sparing mastectomy enrolling up to 20 women with early-stage breast cancer or inherited genetic risk factors (but no cancer diagnosis). The trial, sponsored by a Pelotonia Idea Grant and Ohio State, recently enrolled its first patient.

The study’s primary outcomes include the feasibility of removal of the breast tissue en bloc; however, none of the outcomes are classic oncologic metrics such as progression-free survival.

The en bloc removal outcome is in direct response to the FDA’s concerns about minimally invasive cancer surgeries in women, Dr. Park said in an interview. The pilot trial has an investigational device exemption (IDE) granted by the FDA.

“The reason why we can’t just open a randomized controlled study (of robot versus open) and measure oncologic outcomes like recurrence-free survival is because, before we get to that point, we have to make sure” basic safety issues are addressed and established, she explained.

But Dr. Noorchashm said that argument is missing the larger, more important point: “They are still doing an oncologic procedure – you are still obliged to do noninferiority [randomized] testing with respect to cancer outcomes.”

Dr. Park sounded a different note: “We are doing it as safely as we can do it.”
 

Prophylactic use is also a cancer surgery

Intuitive’s five-center trial does not include en bloc removal of the breast gland as a primary outcome. Instead, the two primary outcomes are conversions to open mastectomy (efficacy measure) and the incidence of adverse events during surgery to 42 days after surgery (safety measure).

The company’s trial does not include any women with breast cancer, but is limited to women at increased risk for breast cancer and seeking prophylactic nipple-sparing mastectomy surgery.

Enrollment in the 145-patient single-arm trial began in the last few months and has a primary completion date of December 2022. It also has an IDE from the FDA.

“I do think that things like this need to be done with caution,” said Katherine Kopkash, MD, an investigator in the Intuitive trial and a breast surgeon at NorthShore University HealthSystem in Evanston, Ill., referring to the trial’s FDA exemption.  

Dr. Kopkash said in an interview that the researchers in the multisite, single-arm Intuitive trial will also track oncologic outcomes, but the trial description at clinicaltrials.gov does not indicate that.

Both Dr. Kopkash and Dr. Park cited the high-profile missteps that took place in 2018 at Monmouth County Medical Center in Long Branch, N.J., during what was described as the first-ever use of robotic nipple-sparing mastectomy for invasive cancer in the United States, as reported by Medscape Medical News. However, neither the center or surgeon, Stephen Chagares, MD, requested or received an IDE from the FDA, and use of robotic mastectomy was halted after two cases.

It’s conceivable that Intuitive will seek out FDA clearance for use of its da Vinci system in robotic nipple-sparing mastectomy with data in a prophylactic setting and then expand the pool of patients, argued Dr. Noorchashm.

“Even if you introduce a new technology ... for a narrow subset of patients, the application of it eventually occurs on a ‘sliding scale,’ ” he said.

The former surgeon gave an example: The first device used in gastric bypass surgery was cleared for use in 2001 by the FDA for adults who were “severely morbidly obese.” But by the late 2000s, the operation was also being performed on people with lower body mass indexes who hadn’t exhausted traditional weight loss procedures. “It was very lucrative,” Dr. Noorchashm said about the surgery.
 

Surgeons only get one body

Intuitive has been hugely successful in developing and marketing its da Vinci system around the world for general and oncologic surgeries, with more than 1 million surgeries in 2018, a greater than sevenfold increase in 10 years, according to the authors of a new essay published in the June issue of the Annals of Surgery. The authors include breast surgeon Rosa F. Hwang, MD, of MD Anderson Cancer Center in Houston, who is also an investigator for the Intuitive trial.

However, robotic mastectomy is still a new surgery – only about 150 patients have been treated in the world, mostly in Italy, France, Taiwan, and Korea, the authors noted.

Despite such small numbers, “there’s a lot of interest in bringing this to the United States,” said Dr. Park.

One of the arguments in favor of robotic mastectomy for nipple-sparing procedures has nothing to do with patients. Instead, it is improved ergonomics – the robot makes a tough surgery easier on the surgeon.

Even stalwart robot critic Dr. Margenthaler conceded that this was possibly a winning feature.

“Nipple-sparing mastectomy is a very physically demanding procedure for the surgeon, resulting in higher rates of neck and back pain and fatigue compared with a standard skin-sparing approach,” she noted. She suggested, however, that practitioners of traditional mastectomy ought to first experiment with changes to patient positioning and incision placement to alleviate stress before looking to the robot for change.

When this news organization interviewed NorthShore University’s Dr. Kopkash, she had conducted four nipple-sparing mastectomies in the previous week. “It’s a difficult procedure on our bodies. I just turned 40 and I’m considered young for a surgeon. We get one body for our career and we have to figure out ways to make it work and protect it.”

Intuitive Surgical is funding the five-center clinical trial of robot-assisted nipple-sparing mastectomy, and UT Southwestern is funding its own trial. The Ohio State trial is funded by the university and a Pelotonia Idea Grant. Dr. Noorchashm and Dr. Margenthaler have no relevant financial disclosures.

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

Overall cancer mortality in females continues to decrease in the United States, but “previous declining trends in death rates slowed” for breast cancer in recent years, according to an annual report by several national organizations.

The analysis of long-term trends in cancer death rates shows that a decline of 1.4% per year from 2001 to 2016 accelerated to 2.1% per year in 2016-2018, the American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, and the North American Association of Central Cancer Registries said.

Decreases in overall cancer mortality were seen in females of all races and ethnic groups over the most recent 5-year period included in the report, 2014-2018, varying from –1.6% per year in both non-Hispanic Blacks and Whites to –0.9% for non-Hispanic American Indians/Alaska Natives (AI/ANs), Farhad Islami, MD, PhD, of the American Cancer Society, Atlanta, and associates said in the Journal of the National Cancer Institute.

Over those 5 years, death rates fell for 14 of the 20 most common cancers in females; increased for liver, uterus, brain, pancreas, and soft tissue including heart; and remained stable for cancers of the oral cavity/pharynx, they reported.

Breast cancer was among those that declined, but the rate of that decline has been slowing. Mortality declined by an average of 2.3% per year in 2003-2007, by 1.6% a year in 2007-2014, and by just 1.0% annually during 2014-2018, based on data from the National Center for Health Statistics’ National Vital Statistics System.

Mortality from all cancers in 2014-2018 was 133.5 deaths per 100,000 standard population, with the racial/ethnic gap ranging from 85.4 per 100,000 (non-Hispanic Asian/Pacific Islander) to 154.9 (non-Hispanic Black), Dr. Islami and associates said.

Melanoma had the largest decline in mortality over that period among the 20 most common cancers in females, falling by an average of 4.4% per year, with lung cancer next at 4.3%. Among those with increased death rates, uterine cancer saw the largest rise at 2.0% a year, the research team said.

The deaths caused by cancer of the uterus were most common in non-Hispanic Black females, 8.9 per 100,000 population, followed by non-Hispanic White (4.5), Hispanic (4.1), non-Hispanic AI/AN (4.0), and non-Hispanic Asian/Pacific Islander (3.3), they reported.

“Long-term increasing trends in uterine cancer death rates parallel trends in incidence, although death rates are increasing at a somewhat faster rate. Increasing uterine cancer incidence has been attributed to increasing obesity prevalence and decreased use of combined hormone replacement therapy,” Dr. Islami and associates pointed out.

Breast cancer deaths also were most common among Blacks in 2014-2018, occurring at a rate of 28.2 per 100,000, as were deaths from cancer of the cervix (3.4 per 100,000), while ovarian cancers deaths were highest in White females (7.1 per 100,000), the researchers noted.

The continuing racial and ethnic disparity “largely reflects a combination of multiple intertwined factors” of tumor biology, diagnosis, treatment, and systemic discrimination, they wrote, adding that Black persons “are more likely to have a higher exposure to some cancer risk factors and limited access to healthy food, safe places for physical activity, and evidence-based cancer preventive services.”

The report was funded by the four participating groups. Six of the 12 investigators are employees of the American Cancer Society whose salaries are solely paid by the society; the other authors had no conflicts of interest to disclose.

[email protected]

Overall cancer mortality in females continues to decrease in the United States, but “previous declining trends in death rates slowed” for breast cancer in recent years, according to an annual report by several national organizations.

The analysis of long-term trends in cancer death rates shows that a decline of 1.4% per year from 2001 to 2016 accelerated to 2.1% per year in 2016-2018, the American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, and the North American Association of Central Cancer Registries said.

Decreases in overall cancer mortality were seen in females of all races and ethnic groups over the most recent 5-year period included in the report, 2014-2018, varying from –1.6% per year in both non-Hispanic Blacks and Whites to –0.9% for non-Hispanic American Indians/Alaska Natives (AI/ANs), Farhad Islami, MD, PhD, of the American Cancer Society, Atlanta, and associates said in the Journal of the National Cancer Institute.

Over those 5 years, death rates fell for 14 of the 20 most common cancers in females; increased for liver, uterus, brain, pancreas, and soft tissue including heart; and remained stable for cancers of the oral cavity/pharynx, they reported.

Breast cancer was among those that declined, but the rate of that decline has been slowing. Mortality declined by an average of 2.3% per year in 2003-2007, by 1.6% a year in 2007-2014, and by just 1.0% annually during 2014-2018, based on data from the National Center for Health Statistics’ National Vital Statistics System.

Mortality from all cancers in 2014-2018 was 133.5 deaths per 100,000 standard population, with the racial/ethnic gap ranging from 85.4 per 100,000 (non-Hispanic Asian/Pacific Islander) to 154.9 (non-Hispanic Black), Dr. Islami and associates said.

Melanoma had the largest decline in mortality over that period among the 20 most common cancers in females, falling by an average of 4.4% per year, with lung cancer next at 4.3%. Among those with increased death rates, uterine cancer saw the largest rise at 2.0% a year, the research team said.

The deaths caused by cancer of the uterus were most common in non-Hispanic Black females, 8.9 per 100,000 population, followed by non-Hispanic White (4.5), Hispanic (4.1), non-Hispanic AI/AN (4.0), and non-Hispanic Asian/Pacific Islander (3.3), they reported.

“Long-term increasing trends in uterine cancer death rates parallel trends in incidence, although death rates are increasing at a somewhat faster rate. Increasing uterine cancer incidence has been attributed to increasing obesity prevalence and decreased use of combined hormone replacement therapy,” Dr. Islami and associates pointed out.

Breast cancer deaths also were most common among Blacks in 2014-2018, occurring at a rate of 28.2 per 100,000, as were deaths from cancer of the cervix (3.4 per 100,000), while ovarian cancers deaths were highest in White females (7.1 per 100,000), the researchers noted.

The continuing racial and ethnic disparity “largely reflects a combination of multiple intertwined factors” of tumor biology, diagnosis, treatment, and systemic discrimination, they wrote, adding that Black persons “are more likely to have a higher exposure to some cancer risk factors and limited access to healthy food, safe places for physical activity, and evidence-based cancer preventive services.”

The report was funded by the four participating groups. Six of the 12 investigators are employees of the American Cancer Society whose salaries are solely paid by the society; the other authors had no conflicts of interest to disclose.

[email protected]

Overall cancer mortality in females continues to decrease in the United States, but “previous declining trends in death rates slowed” for breast cancer in recent years, according to an annual report by several national organizations.

The analysis of long-term trends in cancer death rates shows that a decline of 1.4% per year from 2001 to 2016 accelerated to 2.1% per year in 2016-2018, the American Cancer Society, Centers for Disease Control and Prevention, National Cancer Institute, and the North American Association of Central Cancer Registries said.

Decreases in overall cancer mortality were seen in females of all races and ethnic groups over the most recent 5-year period included in the report, 2014-2018, varying from –1.6% per year in both non-Hispanic Blacks and Whites to –0.9% for non-Hispanic American Indians/Alaska Natives (AI/ANs), Farhad Islami, MD, PhD, of the American Cancer Society, Atlanta, and associates said in the Journal of the National Cancer Institute.

Over those 5 years, death rates fell for 14 of the 20 most common cancers in females; increased for liver, uterus, brain, pancreas, and soft tissue including heart; and remained stable for cancers of the oral cavity/pharynx, they reported.

Breast cancer was among those that declined, but the rate of that decline has been slowing. Mortality declined by an average of 2.3% per year in 2003-2007, by 1.6% a year in 2007-2014, and by just 1.0% annually during 2014-2018, based on data from the National Center for Health Statistics’ National Vital Statistics System.

Mortality from all cancers in 2014-2018 was 133.5 deaths per 100,000 standard population, with the racial/ethnic gap ranging from 85.4 per 100,000 (non-Hispanic Asian/Pacific Islander) to 154.9 (non-Hispanic Black), Dr. Islami and associates said.

Melanoma had the largest decline in mortality over that period among the 20 most common cancers in females, falling by an average of 4.4% per year, with lung cancer next at 4.3%. Among those with increased death rates, uterine cancer saw the largest rise at 2.0% a year, the research team said.

The deaths caused by cancer of the uterus were most common in non-Hispanic Black females, 8.9 per 100,000 population, followed by non-Hispanic White (4.5), Hispanic (4.1), non-Hispanic AI/AN (4.0), and non-Hispanic Asian/Pacific Islander (3.3), they reported.

“Long-term increasing trends in uterine cancer death rates parallel trends in incidence, although death rates are increasing at a somewhat faster rate. Increasing uterine cancer incidence has been attributed to increasing obesity prevalence and decreased use of combined hormone replacement therapy,” Dr. Islami and associates pointed out.

Breast cancer deaths also were most common among Blacks in 2014-2018, occurring at a rate of 28.2 per 100,000, as were deaths from cancer of the cervix (3.4 per 100,000), while ovarian cancers deaths were highest in White females (7.1 per 100,000), the researchers noted.

The continuing racial and ethnic disparity “largely reflects a combination of multiple intertwined factors” of tumor biology, diagnosis, treatment, and systemic discrimination, they wrote, adding that Black persons “are more likely to have a higher exposure to some cancer risk factors and limited access to healthy food, safe places for physical activity, and evidence-based cancer preventive services.”

The report was funded by the four participating groups. Six of the 12 investigators are employees of the American Cancer Society whose salaries are solely paid by the society; the other authors had no conflicts of interest to disclose.

[email protected]

More than 280,000 women in the United States will be diagnosed with invasive breast cancer this year. For those with metastatic breast cancer with distant spread, the 5-year survival rate is approximately 28%. Whether advanced disease is discovered at initial diagnosis or in relapsed disease, it is imperative to understand the molecular characteristics of the metastatic tumor.

Dr Susan Domchek, from the University of Pennsylvania, discusses the importance of retesting for estrogen receptor, progesterone receptor, and HER2/neu on a metastatic tumor focus in order to identify potential discordance between the primary cancer and metastatic disease.

Additionally, Dr Domchek discusses the importance of molecular testing for targetable mutations, including P13K and germline BRCA1/2, for which approved therapies have shown survival benefit.

The list of targetable mutations in breast cancer continues to expand. In the tumor-agnostic studies, pembrolizumab has shown survival benefit in tumors that have mismatch repair deficiency and microsatellite instability, and TRK inhibitors have shown efficacy in tumors positive for NTRK fusions. Numerous clinical trials are available looking at additional molecular-based therapies.

--

Susan M. Domchek, MD, Basser Professor, Department of Oncology; Executive Director, Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia.

Susan M. Domchek, MD, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from: AstraZeneca; Clovis; Bristol Myers Squibb.

More than 280,000 women in the United States will be diagnosed with invasive breast cancer this year. For those with metastatic breast cancer with distant spread, the 5-year survival rate is approximately 28%. Whether advanced disease is discovered at initial diagnosis or in relapsed disease, it is imperative to understand the molecular characteristics of the metastatic tumor.

Dr Susan Domchek, from the University of Pennsylvania, discusses the importance of retesting for estrogen receptor, progesterone receptor, and HER2/neu on a metastatic tumor focus in order to identify potential discordance between the primary cancer and metastatic disease.

Additionally, Dr Domchek discusses the importance of molecular testing for targetable mutations, including P13K and germline BRCA1/2, for which approved therapies have shown survival benefit.

The list of targetable mutations in breast cancer continues to expand. In the tumor-agnostic studies, pembrolizumab has shown survival benefit in tumors that have mismatch repair deficiency and microsatellite instability, and TRK inhibitors have shown efficacy in tumors positive for NTRK fusions. Numerous clinical trials are available looking at additional molecular-based therapies.

--

Susan M. Domchek, MD, Basser Professor, Department of Oncology; Executive Director, Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia.

Susan M. Domchek, MD, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from: AstraZeneca; Clovis; Bristol Myers Squibb.

More than 280,000 women in the United States will be diagnosed with invasive breast cancer this year. For those with metastatic breast cancer with distant spread, the 5-year survival rate is approximately 28%. Whether advanced disease is discovered at initial diagnosis or in relapsed disease, it is imperative to understand the molecular characteristics of the metastatic tumor.

Dr Susan Domchek, from the University of Pennsylvania, discusses the importance of retesting for estrogen receptor, progesterone receptor, and HER2/neu on a metastatic tumor focus in order to identify potential discordance between the primary cancer and metastatic disease.

Additionally, Dr Domchek discusses the importance of molecular testing for targetable mutations, including P13K and germline BRCA1/2, for which approved therapies have shown survival benefit.

The list of targetable mutations in breast cancer continues to expand. In the tumor-agnostic studies, pembrolizumab has shown survival benefit in tumors that have mismatch repair deficiency and microsatellite instability, and TRK inhibitors have shown efficacy in tumors positive for NTRK fusions. Numerous clinical trials are available looking at additional molecular-based therapies.

--

Susan M. Domchek, MD, Basser Professor, Department of Oncology; Executive Director, Basser Center for BRCA, Abramson Cancer Center, University of Pennsylvania, Philadelphia.

Susan M. Domchek, MD, has disclosed the following relevant financial relationships: Received income in an amount equal to or greater than $250 from: AstraZeneca; Clovis; Bristol Myers Squibb.