Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer

Minckwitz, Gϋnter von; Huang, Chiun‐Sheng; Mano, Max S.; Loibl, Sibylle; Mamounas, Eleftherios P.; Untch, Michael; Wolmark, Norman; Rastogi, Priya; Schneeweiß, Andreas; Redondo, Andrés; Fischer, Hans Holger; Jacot, William; Conlin, Alison; Arce-Salinas, Claudia; Wapnir, Irene; Jackisch, Christian; DiGiovanna, Michael P.; Fasching, Peter A.; Crown, John; Wülfing, P.; Shao, Zhimin; Caremoli, Elena Rota; Wu, Haiyan; Lam, Lisa H.; Tesarowski, David; Smitt, Melanie C.; Douthwaite, Hannah; Singel, Stina Mui; Geyer, Charles E.

doi:10.1056/nejmoa1814017

Cited by 1,955 publications

(1,572 citation statements)

References 18 publications

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“…The extent of residual disease at the time of surgery (ie, pathologic response) provides important prognostic information and may inform additional therapeutic recommendations. Recent research has focused on identifying therapies that can improve outcomes among patients with breast cancer who receive neoadjuvant treatment but fail to achieve a complete pathologic response …”

Section: Selected Findingsmentioning

confidence: 99%

“…Recent research has focused on identifying therapies that can improve outcomes among patients with breast cancer who receive neoadjuvant treatment but fail to achieve a complete pathologic response. 51,52 Treatment advances for HR-negative/HER2-negative breast cancers have lagged behind those for other molecular subtypes and thus far have been limited to chemotherapy for nonmetastatic disease. 53 However, immunotherapy drugs are an emerging area of breast cancer treatment, particularly for patients with this subtype.…”

Section: Treatmentmentioning

confidence: 99%

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Breast cancer statistics, 2019

DeSantis

Gaudet

et al. 2019

CA A Cancer J Clinicians

2,535

1,881

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This article is the American Cancer Society’s biennial update on female breast cancer statistics in the United States, including data on incidence, mortality, survival, and screening. Over the most recent 5‐year period (2012‐2016), the breast cancer incidence rate increased slightly by 0.3% per year, largely because of rising rates of local stage and hormone receptor‐positive disease. In contrast, the breast cancer death rate continues to decline, dropping 40% from 1989 to 2017 and translating to 375,900 breast cancer deaths averted. Notably, the pace of the decline has slowed from an annual decrease of 1.9% during 1998 through 2011 to 1.3% during 2011 through 2017, largely driven by the trend in white women. Consequently, the black–white disparity in breast cancer mortality has remained stable since 2011 after widening over the past 3 decades. Nevertheless, the death rate remains 40% higher in blacks (28.4 vs 20.3 deaths per 100,000) despite a lower incidence rate (126.7 vs 130.8); this disparity is magnified among black women aged <50 years, who have a death rate double that of whites. In the most recent 5‐year period (2013‐2017), the death rate declined in Hispanics (2.1% per year), blacks (1.5%), whites (1.0%), and Asians/Pacific Islanders (0.8%) but was stable in American Indians/Alaska Natives. However, by state, breast cancer mortality rates are no longer declining in Nebraska overall; in Colorado and Wisconsin in black women; and in Nebraska, Texas, and Virginia in white women. Breast cancer was the leading cause of cancer death in women (surpassing lung cancer) in four Southern and two Midwestern states among blacks and in Utah among whites during 2016‐2017. Declines in breast cancer mortality could be accelerated by expanding access to high‐quality prevention, early detection, and treatment services to all women.

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Section: Selected Findingsmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

Breast cancer statistics, 2019

DeSantis

Gaudet

et al. 2019

CA A Cancer J Clinicians

2,535

1,881

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“…The role of adjuvant systemic treatment after NACT and definitive surgery in patients who do not achieve pCR is also emerging. The recently published CREATE‐X and KATHERINE studies reported disease free survival improvements when additional adjuvant systemic treatment is applied to patients with residual disease in the triple negative and HER2 positive breast cancer subgroups . Such novel strategies to improve patient outcome will likely encourage further utilisation of NACT as a treatment paradigm.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant chemotherapy in non‐metastatic breast cancer: a study on practice trends in a regional cancer treatment service

Ang

Wewala

Carroll

et al. 2020

Internal Medicine Journal

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Background Neoadjuvant chemotherapy (NACT) is increasingly used for managing locally advanced and high risk non‐metastatic breast cancer. Aims To describe trends in NACT use, assess compliance to best practice recommendations and determine treatment response rates in a regional cancer treatment service. Methods In this retrospective cross‐ sectional study, electronic records of patients who underwent NACT in centres covered by the MidCentral Regional Cancer Treatment Service in 2013 and 2017 were reviewed. Data pertaining to patient demographics, disease status, compliance to best practice recommendations and treatment outcomes were extracted and analysed. Results Of a total of 502 referrals for non‐metastatic breast cancer, 34 underwent NACT with the estimated NACT rate rising from 3.85% (2013) to 9.92% (2017). Compliance to practice recommendations improved in all domains (pre‐treatment tumour and axillary evaluation, marker placement, multidisciplinary discussion). Overall, NACT was well tolerated with only three patients experiencing treatment limiting toxicity. Response rates mirror published data (complete response: 29.4%, partial: 61.8%) with higher responses registered in HER2 positive and triple negative subtypes. Discordance between radiological and pathological response was 28%, with imaging overestimating response in five out of seven cases. Of the 11 (32%) patients who initially underwent breast conserving surgery, six required a second surgery. Conclusion NACT is increasingly used in the Regional Cancer Treatment Service, with improving compliance to practice recommendations. These results are reassuring and can be used to help patients develop a realistic expectation towards NACT.

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“…21 Especially for high-risk patients, such as those in the current study (>96% node-positive and >40% with at least 4 positive nodes), there is an unmet need despite anti-HER2 treatment, as indicated by the 10-year disease-free survival rates in the HERA trial of 74.5% for patients with 1 to 3 positive nodes and 54.5% for patients with 4 or more positive nodes who received 1 year of adjuvant trastuzumab. 22 Since the demonstration that further adjuvant trastuzumab emtansine improves the prognosis of patients not achieving pathologic complete remission with neoadjuvant chemotherapy, 23 treating patients with locally advanced HER2-positive disease preoperatively has been recommended. 23,24 However, real-world data show that neoadjuvant therapy is vastly underused both in developed countries and in developing countries, and this underscores the value of optimizing adjuvant strategies.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of tailored and dose‐dense adjuvant chemotherapy and trastuzumab for resected HER2‐positive breast cancer: Results from the phase 3 PANTHER trial

Papakonstantinou

Matikas

Bengtsson³

et al. 2019

Cancer

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Background Dose‐dense (DD) adjuvant chemotherapy improves outcomes in early breast cancer (BC). However, there are no phase 3 randomized data to inform on its combination with trastuzumab for patients with human epidermal growth factor receptor 2 (HER2)–positive disease. Methods This was a protocol‐predefined secondary analysis of the randomized phase 3 Pan‐European Tailored Chemotherapy (PANTHER) trial. Women 65 years old or younger with node‐positive or high‐risk, node‐negative BC were randomized 1:1 to either tailored (according to hematologic nadirs) and DD epirubicin and cyclophosphamide followed by docetaxel or standard 5‐fluorouracil, epirubicin, and cyclophosphamide plus docetaxel every 3 weeks. Patients with HER2‐positive disease received 1 year of adjuvant trastuzumab. The primary endpoint was BC relapse–free survival. In addition, HER2‐positive patients and an equal number of HER2‐negative patients matched for age, treatment group, and institution who were enrolled at Swedish sites were asked to participate in a predefined study of cardiac safety and underwent echocardiography or multigated acquisition scanning and electrocardiography at the baseline and at 4 and 6 years of follow‐up. Results There were 342 HER2‐positive patients; 335 received at least 1 dose of trastuzumab, and 29 patients discontinued trastuzumab prematurely. Relapse‐free survival was not statistically significantly in favor of the tailored and DD group (hazard ratio, 0.68; 95% confidence interval, 0.37‐1.27; P = .231). Cardiac outcomes after 4 and 6 years of follow‐up did not differ significantly between HER2‐positive and HER2‐negative patients or between the 2 treatment groups. Conclusions The combination of DD chemotherapy and trastuzumab decreased the relative risk for relapse by 32% in comparison with standard treatment, a statistically nonsignificant difference. Its efficacy and safety merit further evaluation as part of both escalation and de‐escalation strategies.

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Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer

Cited by 1,955 publications

References 18 publications

Breast cancer statistics, 2019

Breast cancer statistics, 2019

Neoadjuvant chemotherapy in non‐metastatic breast cancer: a study on practice trends in a regional cancer treatment service

Efficacy and safety of tailored and dose‐dense adjuvant chemotherapy and trastuzumab for resected HER2‐positive breast cancer: Results from the phase 3 PANTHER trial

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