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Impact of neoadjuvant chemotherapy in stage II-III triple negative breast cancer on eligibility for breast-conserving surgery and breast conservation rates: surgical results from CALGB 40603 (Alliance).

ABSTRACT: OBJECTIVE:To assess the efficacy of neoadjuvant systemic therapy (NST) at increasing the rate of successful breast-conserving therapy (BCT) in triple negative breast cancer. BACKGROUND:Inducing tumor regression to permit BCT is often cited to support administration of NST. To quantify this benefit, we conducted a surgical companion study to CALGB40603, a randomized phase II, 2×2 factorial trial of neoadjuvant paclitaxel ± carboplatin ± bevacizumab (B) followed by doxorubicin plus cyclophosphamide ± B in stage II-III triple negative breast cancer. METHODS:Before and after NST, treating surgeons evaluated BCT candidacy by clinico-radiographic criteria; surgery performed was at surgeon and patient discretion. We measured (1) conversion rates from BCT-ineligible to BCT-eligible, (2) surgical choices in BCT candidates, and (3) rates of successful BCT with tumor-free margins. RESULTS:Four hundred four patients were assessable for surgical outcomes. Two hundred nineteen (54%) were BCT candidates before NST. One hundred ninety-seven (90%) remained BCT candidates after NST, of whom 138 (70%) chose BCT, which was successful in 130 (94%). Of 185 (46%) who were not BCT candidates before NST, 78 (42%) converted to candidates with NST. Of these, 53 (68%) chose BCT with a 91% (48/53) success rate. The overall BCT-eligibility rate rose from 54% to 68% (275/404) with NST. Addition of carboplatin, B, or both increased conversion rates. CONCLUSIONS:This is the first study to document prospectively a 42% conversion rate from BCT-ineligible to BCT-eligible, resulting in a 14% absolute increase in BCT eligibility. BCT was successful in 93% of patients who opted for it, but 31% of BCT-eligible patients still chose mastectomy.

SUBMITTER: Golshan M

PROVIDER: S-EPMC4710511 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Impact of neoadjuvant chemotherapy in stage II-III triple negative breast cancer on eligibility for breast-conserving surgery and breast conservation rates: surgical results from CALGB 40603 (Alliance).

Golshan Mehra M Cirrincione Constance T CT Sikov William M WM Berry Donald A DA Jasinski Sara S Weisberg Tracey F TF Somlo George G Hudis Clifford C Winer Eric E Ollila David W DW

Annals of surgery 20150901 3

<h4>Objective</h4>To assess the efficacy of neoadjuvant systemic therapy (NST) at increasing the rate of successful breast-conserving therapy (BCT) in triple negative breast cancer.<h4>Background</h4>Inducing tumor regression to permit BCT is often cited to support administration of NST. To quantify this benefit, we conducted a surgical companion study to CALGB40603, a randomized phase II, 2×2 factorial trial of neoadjuvant paclitaxel ± carboplatin ± bevacizumab (B) followed by doxorubicin plus ...[more]

PMID: 26222764

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Project description:ImportanceNeoadjuvant systemic therapy (NST) is often administered to enable breast-conserving therapy (BCT) in stages II to III breast cancer.ObjectivesTo prospectively evaluate the role of NST in conversion from BCT ineligibility to BCT eligibility and to assess the association of response to NST, germline BRCA (gBRCA) status, and region of treatment with surgical choice in women with triple-negative breast cancer (TNBC).Design, setting, and participantsThis prespecified secondary analysis of a multicentered, phase 3, double-blind, randomized clinical trial (BrighTNess) enrolled 634 eligible women across 145 centers in 15 countries in North America, Europe, and Asia. Women with operable, clinical stages II to III TNBC who underwent gBRCA mutation testing before initiating NST were eligible to participate. Data were collected from April 1, 2014, to December 8, 2016. This preplanned analysis was performed from January 5, 2018, to October 28, 2019.InterventionsStudy participants were randomized to receive 12 weeks of weekly paclitaxel alone or with the addition of carboplatin and/or veliparib, followed by 4 cycles of doxorubicin hydrochloride and cyclophosphamide.Main outcomes and measuresSurgeons assessed BCT candidacy by clinical and radiographic criteria before and after NST. Surgical choices and whether BCT eligibility was associated with the likelihood of pathologic complete response were then analyzed.ResultsAmong the 634 randomized patients (median age, 51 [range, 22-78] years), pre- and post-NST assessments were available for 604 patients. Of 141 patients deemed BCT ineligible at baseline, 75 (53.2%) converted to BCT eligible. Overall, 342 (68.1%) of 502 patients deemed BCT eligible after NST underwent BCT, including 42 (56.0%) of the 75 who converted to BCT eligible. Patients treated in Europe and Asia were more likely to undergo BCT (odds ratio, 2.66; 95% CI, 1.84-3.84) compared with those treated in North America. Among patients without gBRCA mutation undergoing mastectomy, those treated in North America were more likely to undergo contralateral prophylactic mastectomy (57 of 81 [70.4%] vs 6 of 30 [20.0%]; P < .001). Rates of pathologic complete response were similar between patients deemed BCT eligible at baseline and those who were BCT ineligible but converted to BCT eligibility after NST (55.3 [235 of 425] vs 49.3% [37 of 75]; P = .38).Conclusions and relevanceThis prospective analysis of NST and BCT eligibility in TNBC demonstrates a conversion from BCT ineligibility to BCT eligibility of 53.2%. Lower BCT rates among eligible patients and higher bilateral mastectomy rates among patients without gBRCA mutation in North America merit investigation.Trial registrationClinicalTrials.gov identifier: NCT02032277.

Project description:PurposeOne third of patients with triple-negative breast cancer (TNBC) achieve pathologic complete response (pCR) with standard neoadjuvant chemotherapy (NACT). CALGB 40603 (Alliance), a 2 × 2 factorial, open-label, randomized phase II trial, evaluated the impact of adding carboplatin and/or bevacizumab.Patients and methodsPatients (N = 443) with stage II to III TNBC received paclitaxel 80 mg/m(2) once per week (wP) for 12 weeks, followed by doxorubicin plus cyclophosphamide once every 2 weeks (ddAC) for four cycles, and were randomly assigned to concurrent carboplatin (area under curve 6) once every 3 weeks for four cycles and/or bevacizumab 10 mg/kg once every 2 weeks for nine cycles. Effects of adding these agents on pCR breast (ypT0/is), pCR breast/axilla (ypT0/isN0), treatment delivery, and toxicities were analyzed.ResultsPatients assigned to either carboplatin or bevacizumab were less likely to complete wP and ddAC without skipped doses, dose modification, or early discontinuation resulting from toxicity. Grade ≥ 3 neutropenia and thrombocytopenia were more common with carboplatin, as were hypertension, infection, thromboembolic events, bleeding, and postoperative complications with bevacizumab. Employing one-sided P values, addition of either carboplatin (60% v 44%; P = .0018) or bevacizumab (59% v 48%; P = .0089) significantly increased pCR breast, whereas only carboplatin (54% v 41%; P = .0029) significantly raised pCR breast/axilla. More-than-additive interactions between the two agents could not be demonstrated.ConclusionIn stage II to III TNBC, addition of either carboplatin or bevacizumab to NACT increased pCR rates, but whether this will improve relapse-free or overall survival is unknown. Given results from recently reported adjuvant trials, further investigation of bevacizumab in this setting is unlikely, but the role of carboplatin could be evaluated in definitive studies, ideally limited to biologically defined patient subsets most likely to benefit from this agent.

Dataset Information

Impact of neoadjuvant chemotherapy in stage II-III triple negative breast cancer on eligibility for breast-conserving surgery and breast conservation rates: surgical results from CALGB 40603 (Alliance).

Publications

Impact of neoadjuvant chemotherapy in stage II-III triple negative breast cancer on eligibility for breast-conserving surgery and breast conservation rates: surgical results from CALGB 40603 (Alliance).

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