Skip to main content
Top
Published in: Breast Cancer Research and Treatment 2/2016

01-11-2016 | Clinical trial

Impact of neoadjuvant therapy on eligibility for and frequency of breast conservation in stage II–III HER2-positive breast cancer: surgical results of CALGB 40601 (Alliance)

Authors: Mehra Golshan, Constance T. Cirrincione, William M. Sikov, Lisa A. Carey, Donald A. Berry, Beth Overmoyer, Nora L. Henry, George Somlo, Elisa Port, Harold J. Burstein, Clifford Hudis, Eric Winer, David W. Ollila, for the Alliance for Clinical Trials in Oncology

Published in: Breast Cancer Research and Treatment | Issue 2/2016

Login to get access

Abstract

Objective

It had been previously shown that patients who receive neoadjuvant systemic therapy (NST) are more likely to undergo breast-conserving therapy (BCT) than those who have primary surgery. However, the frequency with which patients who are not BCT-eligible prior to NST convert to BCT-eligible with treatment is unknown. To document this conversion rate in a subset of patients expected to have a high clinical response rate to NST, we studied surgical assessment and management of patients enrolled on a randomized neoadjuvant trial for stage II–III HER2-positive breast cancer (HER2 + BC)(CALGB 40601).

Methods

The treating surgeon assessed BCT candidacy based on clinico-radiographic criteria both before and after NST. Definitive breast surgical management was at surgeon and patient discretion. We sought to determine (1) the conversion rate from BCT-ineligible to BCT-eligible (2) the percentage of BCT-eligible patients who chose breast conservation, and (3) the rate of successful BCT. We also evaluated surgeon-determined factors for BCT-ineligibility and the correlation between BCT eligibility and pathologic complete response (pCR).

Results

Of 292 patients with pre- and post-NST surgical assessments, 59 % were non-BCT candidates at baseline. Of the 43 % of these patients who converted with NST, 67 % opted for BCT, with an 80 % success rate. NST increased the BCT-eligible rate from 41 to 64 %. Common factors cited for BCT-ineligibility prior to NST including tumor size (56 %) and probable poor cosmetic outcome (26 %) were reduced by 67 and 75 %, respectively, with treatment, while multicentricity, the second most common factor (33 %), fell by only 16 %. Since 23 % of the BCT-eligible patients chose mastectomy, BCT was the final surgical procedure in just 40 % of the patients. Patients considered BCT-eligible both at baseline and after NST had a pCR rate of 55 %, while patients who were BCT-ineligible prior to NST had the same pCR rate (44 %) whether they converted to BCT-eligible or not.

Conclusions

Many patients with HER2 + BC deemed ineligible for BCT at baseline can be converted to BCT-eligible with NST; excluding patients with multicentric disease substantially increases that percentage. In converted patients who opt for BCT, the success rate is similar to that of patients considered BCT-eligible at baseline. Whether a BCT-ineligible patient converts to BCT eligibility or not does not appear to affect the likelihood of achieving a pCR. Despite the efficacy of NST in this patient cohort, only 40 % of patients had successful BCT; further research into why BCT-eligible patients often opt for mastectomy is needed.
Literature
1.
go back to reference Barry PA, Schiavon G (2015) Primary systemic treatment in the management of operable breast cancer: best surgical approach for diagnosis, biological evaluation, and research. J Natl Cancer Inst Monogr 2015(51):4–8CrossRefPubMed Barry PA, Schiavon G (2015) Primary systemic treatment in the management of operable breast cancer: best surgical approach for diagnosis, biological evaluation, and research. J Natl Cancer Inst Monogr 2015(51):4–8CrossRefPubMed
2.
go back to reference Mauri D, Pavlidis N, Ioannidis JP (2005) Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst 97(3):188–194CrossRefPubMed Mauri D, Pavlidis N, Ioannidis JP (2005) Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst 97(3):188–194CrossRefPubMed
3.
go back to reference Rastogi P, Anderson SJ, Bear HD et al (2008) Preoperative chemotherapy: updates of National surgical adjuvant breast and bowel project protocols B-18 and B-27. J Clin Oncol Off J Am Soc Clin Oncol 26(5):778–785CrossRef Rastogi P, Anderson SJ, Bear HD et al (2008) Preoperative chemotherapy: updates of National surgical adjuvant breast and bowel project protocols B-18 and B-27. J Clin Oncol Off J Am Soc Clin Oncol 26(5):778–785CrossRef
4.
go back to reference van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L (2001) Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol Off J Am Soc Clin Oncol 19(22):4224–4237 van der Hage JA, van de Velde CJ, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L (2001) Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol Off J Am Soc Clin Oncol 19(22):4224–4237
5.
go back to reference Golshan M, Cirrincione CT, Sikov WM et al (2015) 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). Ann Surg 262(3):434–439CrossRefPubMedPubMedCentral Golshan M, Cirrincione CT, Sikov WM et al (2015) 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). Ann Surg 262(3):434–439CrossRefPubMedPubMedCentral
6.
go back to reference Carey LA, Berry DA, Cirrincione CT, Barry WT, Pitcher BN, Harris LN, Ollila DW, Krop IE, Henry NL, Weckstein DJ, Anders CK, Singh B, Hoadley KA, Iglesia M, Cheang MC, Perou CM, Winer EP, Hudis CA (2016) Molecular heterogeneity and response to neoadjuvant human epidermal growth factor receptor 2 targeting in CALGB 40601, a randomized phase III trial of paclitaxel plus trastuzumab with or without lapatinib. J Clin Oncol 34(6):542–549CrossRefPubMed Carey LA, Berry DA, Cirrincione CT, Barry WT, Pitcher BN, Harris LN, Ollila DW, Krop IE, Henry NL, Weckstein DJ, Anders CK, Singh B, Hoadley KA, Iglesia M, Cheang MC, Perou CM, Winer EP, Hudis CA (2016) Molecular heterogeneity and response to neoadjuvant human epidermal growth factor receptor 2 targeting in CALGB 40601, a randomized phase III trial of paclitaxel plus trastuzumab with or without lapatinib. J Clin Oncol 34(6):542–549CrossRefPubMed
7.
go back to reference Criscitiello C, Azim HA, de Azambuja E, Rubio IT (2014) Factors affecting surgical management following neoadjuvant therapy in patients with primary HER2-positive breast cancer: results from the NeoALTTO phase III trial. Ann Oncol Off J Eur Soc Med Oncol ESMO 25(4):910–911CrossRef Criscitiello C, Azim HA, de Azambuja E, Rubio IT (2014) Factors affecting surgical management following neoadjuvant therapy in patients with primary HER2-positive breast cancer: results from the NeoALTTO phase III trial. Ann Oncol Off J Eur Soc Med Oncol ESMO 25(4):910–911CrossRef
8.
go back to reference von Minckwitz G, Schneeweiss A, Loibl S et al (2014) Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol 15(7):747–756CrossRef von Minckwitz G, Schneeweiss A, Loibl S et al (2014) Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol 15(7):747–756CrossRef
9.
go back to reference Debled M, MacGrogan G, Breton-Callu C et al (2015) Surgery following neoadjuvant chemotherapy for HER2-positive locally advanced breast cancer. Time to reconsider the standard attitude. Eur J Cancer 51(6):697–704CrossRefPubMed Debled M, MacGrogan G, Breton-Callu C et al (2015) Surgery following neoadjuvant chemotherapy for HER2-positive locally advanced breast cancer. Time to reconsider the standard attitude. Eur J Cancer 51(6):697–704CrossRefPubMed
10.
go back to reference Holmes D, Colfry A, Czerniecki B et al (2015) Performance and practice guideline for the use of neoadjuvant systemic therapy in the management of breast cancer. Ann Surg Oncol 22(10):3184–3190CrossRefPubMed Holmes D, Colfry A, Czerniecki B et al (2015) Performance and practice guideline for the use of neoadjuvant systemic therapy in the management of breast cancer. Ann Surg Oncol 22(10):3184–3190CrossRefPubMed
11.
go back to reference McGuire KP, Hwang ES, Cantor A et al (2015) Surgical patterns of care in patients with invasive breast cancer treated with neoadjuvant systemic therapy and breast magnetic resonance imaging: results of a secondary analysis of TBCRC 017. Ann Surg Oncol 22(1):75–81CrossRefPubMed McGuire KP, Hwang ES, Cantor A et al (2015) Surgical patterns of care in patients with invasive breast cancer treated with neoadjuvant systemic therapy and breast magnetic resonance imaging: results of a secondary analysis of TBCRC 017. Ann Surg Oncol 22(1):75–81CrossRefPubMed
12.
go back to reference Caudle AS, Yu TK, Tucker SL et al (2012) Local-regional control according to surrogate markers of breast cancer subtypes and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast conserving therapy. Breast Cancer Res BCR 14(3):R83CrossRefPubMed Caudle AS, Yu TK, Tucker SL et al (2012) Local-regional control according to surrogate markers of breast cancer subtypes and response to neoadjuvant chemotherapy in breast cancer patients undergoing breast conserving therapy. Breast Cancer Res BCR 14(3):R83CrossRefPubMed
13.
go back to reference Cureton EL, Yau C, Alvarado MD et al (2014) Local recurrence rates are low in high-risk neoadjuvant breast cancer in the I-SPY 1 Trial (CALGB 150007/150012; ACRIN 6657). Ann Surg Oncol 21(9):2889–2896CrossRefPubMedPubMedCentral Cureton EL, Yau C, Alvarado MD et al (2014) Local recurrence rates are low in high-risk neoadjuvant breast cancer in the I-SPY 1 Trial (CALGB 150007/150012; ACRIN 6657). Ann Surg Oncol 21(9):2889–2896CrossRefPubMedPubMedCentral
14.
go back to reference Kummel S, Holtschmidt J, Loibl S (2014) Surgical treatment of primary breast cancer in the neoadjuvant setting. Br J Surg 101(8):912–924CrossRefPubMed Kummel S, Holtschmidt J, Loibl S (2014) Surgical treatment of primary breast cancer in the neoadjuvant setting. Br J Surg 101(8):912–924CrossRefPubMed
15.
go back to reference Rippy EE, Ainsworth R, Sathananthan D, Kollias J, Bochner M, Whitfield R (2014) Influences on decision for mastectomy in patients eligible for breast conserving surgery. Breast 23(3):273–278CrossRefPubMed Rippy EE, Ainsworth R, Sathananthan D, Kollias J, Bochner M, Whitfield R (2014) Influences on decision for mastectomy in patients eligible for breast conserving surgery. Breast 23(3):273–278CrossRefPubMed
Metadata
Title
Impact of neoadjuvant therapy on eligibility for and frequency of breast conservation in stage II–III HER2-positive breast cancer: surgical results of CALGB 40601 (Alliance)
Authors
Mehra Golshan
Constance T. Cirrincione
William M. Sikov
Lisa A. Carey
Donald A. Berry
Beth Overmoyer
Nora L. Henry
George Somlo
Elisa Port
Harold J. Burstein
Clifford Hudis
Eric Winer
David W. Ollila
for the Alliance for Clinical Trials in Oncology
Publication date
01-11-2016
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 2/2016
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-016-4006-6

Other articles of this Issue 2/2016

Breast Cancer Research and Treatment 2/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine