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Erschienen in: Annals of Surgical Oncology 13/2023

05.10.2023 | Breast Oncology

Mutational Status is Associated with a Higher Rate of Pathologic Complete Response After Neoadjuvant Chemotherapy in Hormone Receptor-Positive Breast Cancer

verfasst von: Sara P. Myers, MD, PhD, Varadan Sevilimedu, MBBS, DrPH, Andrea V. Barrio, MD, Audree B. Tadros, MD, Anita Mamtani, MD, Mark E. Robson, MD, Monica Morrow, MD, Minna K. Lee, MD

Erschienen in: Annals of Surgical Oncology | Ausgabe 13/2023

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Abstract

Background

Pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) occurs in up to 20% of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) breast cancers. Whether this differs among BRCA mutation carriers is uncertain. This study compared pCR between BRCA1/2 mutation carriers and matched sporadic control subjects.

Methods

From November 2013 to January 2022, this study identified 522 consecutive women with clinical stage I to III HR+/HER2− breast cancer treated with NAC and surgery. The study matched BRCA1/2 mutation carriers 1:2 to non-carriers in terms of age, clinical tumor (cT) and nodal (cN) stage, and differentiation. Two-sample non-parametric tests compared baseline characteristics. Multivariable logistic regression assessed pCR (i.e., ypT0/ispN0) by BRCA1/2 mutational status.

Results

Of the 522 women (median age, 50 years), 59 had BRCA1/2 mutations, 78% of which were clinically node positive. Anthracycline-based NAC was administered to 97%. More BRCA1/2 mutation carriers were younger, had cT1 tumors, and had poorly differentiated disease. After matching, 58 BRCA1/2 mutation carriers were similar to 116 non-carriers in terms of age (p = 0.6), cT (p = 0.9), cN stage (p = 0.7), and tumor differentiation (p > 0.9). Among the mutation carriers, the pCR rate was 15.5% for BRCA1/2, 38% (8/21) for BRCA1, and 2.7% (1/37) for BRCA2 versus 7.8% (9/116) for the non-carriers (p < 0.001). After NAC, 5 (41.7%) of the 12 BRCA1 mutation carriers converted to pN0 versus 10 (37%) of the 27 BRCA2 mutation carriers and 19 (20.9%) of the 91 non-carriers (p = 0.3). In the multivariable analysis, BRCA1 mutation status was associated with higher odds of pCR than non-carrier status (odds ratio [OR] 6.31; 95% confidence interval [CI] 1.95–20.5; p = 0.002), whereas BRCA2 mutation status was not (OR 0.45; 95% CI 0.02–2.67; p = 0.5).

Conclusions

This study showed that BRCA1 mutation carriers with HR+/HER2− breast cancers have a higher rate of pCR than sporadic cancers and may derive greater benefit from chemotherapy. The use of NAC to downstage these patients should be considered.
Literatur
2.
Zurück zum Zitat Byrski T, Gronwald J, Huzarski T, et al. Response to neo-adjuvant chemotherapy in women with BRCA1-positive breast cancers. Breast Cancer Res Treat. 2008;108:289–96.CrossRefPubMed Byrski T, Gronwald J, Huzarski T, et al. Response to neo-adjuvant chemotherapy in women with BRCA1-positive breast cancers. Breast Cancer Res Treat. 2008;108:289–96.CrossRefPubMed
3.
Zurück zum Zitat Chang J, Elledge RM. Clinical management of women with genomic BRCA1 and BRCA2 mutations. Breast Cancer Res Treat. 2001;69:101–13.CrossRefPubMed Chang J, Elledge RM. Clinical management of women with genomic BRCA1 and BRCA2 mutations. Breast Cancer Res Treat. 2001;69:101–13.CrossRefPubMed
4.
Zurück zum Zitat Musolino A, Bella MA, Bortesi B, et al. BRCA mutations, molecular markers, and clinical variables in early-onset breast cancer: a population-based study. Breast. 2007;16:280–92.CrossRefPubMed Musolino A, Bella MA, Bortesi B, et al. BRCA mutations, molecular markers, and clinical variables in early-onset breast cancer: a population-based study. Breast. 2007;16:280–92.CrossRefPubMed
5.
Zurück zum Zitat Tomasello G, Gambini D, Petrelli F, et al. Characterization of the HER2 status in BRCA-mutated breast cancer: a single-institutional series and systematic review with pooled analysis. ESMO Open. 2022;7:100531.CrossRefPubMedPubMedCentral Tomasello G, Gambini D, Petrelli F, et al. Characterization of the HER2 status in BRCA-mutated breast cancer: a single-institutional series and systematic review with pooled analysis. ESMO Open. 2022;7:100531.CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Kennedy RD, Quinn JE, Mullan PB, Johnston PG, Harkin DP. The role of BRCA1 in the cellular response to chemotherapy. J Natl Cancer Inst. 2004;96:1659–68.CrossRefPubMed Kennedy RD, Quinn JE, Mullan PB, Johnston PG, Harkin DP. The role of BRCA1 in the cellular response to chemotherapy. J Natl Cancer Inst. 2004;96:1659–68.CrossRefPubMed
7.
Zurück zum Zitat Lakhani SR, Jacquemier J, Sloane JP, et al. Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. J Natl Cancer Inst. 1998;90:1138–45.CrossRefPubMed Lakhani SR, Jacquemier J, Sloane JP, et al. Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. J Natl Cancer Inst. 1998;90:1138–45.CrossRefPubMed
8.
Zurück zum Zitat Richters LKK, Gluz O, Weber-Lassalle N, et al. Pathological complete response rate and survival in patients with BRCA-associated triple-negative breast cancer after 12 weeks of de-escalated neoadjuvant chemotherapy: translational results of the WSG-ADAPT TN randomized phase II trial (NCT01815242). J Clin Oncol. 2021;39(15 Suppl):579.CrossRef Richters LKK, Gluz O, Weber-Lassalle N, et al. Pathological complete response rate and survival in patients with BRCA-associated triple-negative breast cancer after 12 weeks of de-escalated neoadjuvant chemotherapy: translational results of the WSG-ADAPT TN randomized phase II trial (NCT01815242). J Clin Oncol. 2021;39(15 Suppl):579.CrossRef
9.
Zurück zum Zitat Shah PD, Patil S, Dickler MN, Offit K, Hudis CA, Robson ME. Twenty-one-gene recurrence score assay in BRCA-associated versus sporadic breast cancers: differences based on germline mutation status. Cancer. 2016;122:1178–84.CrossRefPubMed Shah PD, Patil S, Dickler MN, Offit K, Hudis CA, Robson ME. Twenty-one-gene recurrence score assay in BRCA-associated versus sporadic breast cancers: differences based on germline mutation status. Cancer. 2016;122:1178–84.CrossRefPubMed
10.
Zurück zum Zitat Sivina E, Blumberga L, Purkalne G, Irmejs A. Pathological complete response to neoadjuvant chemotherapy in triple-negative breast cancer: single-hospital experience. Hered Cancer Clin Pract. 2023;21:4.CrossRefPubMedPubMedCentral Sivina E, Blumberga L, Purkalne G, Irmejs A. Pathological complete response to neoadjuvant chemotherapy in triple-negative breast cancer: single-hospital experience. Hered Cancer Clin Pract. 2023;21:4.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Wunderle M, Gass P, Häberle L, et al. BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients. Breast Cancer Res Treat. 2018;171:85–94.CrossRefPubMed Wunderle M, Gass P, Häberle L, et al. BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients. Breast Cancer Res Treat. 2018;171:85–94.CrossRefPubMed
12.
Zurück zum Zitat Myers SP, Ahrendt GM, Lee JS, et al. Association of tumor molecular subtype and stage with breast and axillary pathologic complete response after neoadjuvant chemotherapy for breast cancer. Ann Surg Oncol. 2021;28:8636–42.CrossRefPubMed Myers SP, Ahrendt GM, Lee JS, et al. Association of tumor molecular subtype and stage with breast and axillary pathologic complete response after neoadjuvant chemotherapy for breast cancer. Ann Surg Oncol. 2021;28:8636–42.CrossRefPubMed
13.
Zurück zum Zitat Daly MB, Pal T, Berry MP, et al. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic, version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021;19:77–102.CrossRefPubMed Daly MB, Pal T, Berry MP, et al. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic, version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021;19:77–102.CrossRefPubMed
14.
Zurück zum Zitat Bari S, Boulware D, Li J, et al. A real-world data retrospective cohort study of low estrogen receptor-positive early breast cancer: natural history and treatment outcomes. Breast Cancer Dove Med Press. 2022;14:199–210.PubMedPubMedCentral Bari S, Boulware D, Li J, et al. A real-world data retrospective cohort study of low estrogen receptor-positive early breast cancer: natural history and treatment outcomes. Breast Cancer Dove Med Press. 2022;14:199–210.PubMedPubMedCentral
15.
Zurück zum Zitat Guzmán-Arocho YD, Rosenberg SM, Garber JE, et al. Clinicopathological features and BRCA1 and BRCA2 mutation status in a prospective cohort of young women with breast cancer. Br J Cancer. 2022;126:302–9.CrossRefPubMed Guzmán-Arocho YD, Rosenberg SM, Garber JE, et al. Clinicopathological features and BRCA1 and BRCA2 mutation status in a prospective cohort of young women with breast cancer. Br J Cancer. 2022;126:302–9.CrossRefPubMed
16.
Zurück zum Zitat Schrodi S, Braun M, Andrulat A, et al. Outcome of breast cancer patients with low hormone receptor positivity: analysis of a 15-year population-based cohort. Ann Oncol. 2021;32:1410–24.CrossRefPubMed Schrodi S, Braun M, Andrulat A, et al. Outcome of breast cancer patients with low hormone receptor positivity: analysis of a 15-year population-based cohort. Ann Oncol. 2021;32:1410–24.CrossRefPubMed
17.
Zurück zum Zitat Ho D, Imai K, King G, Stuart E. MatchIt: non parametric processing for parametric causal inference. J Stat Software. 2011;42(8):1–28.CrossRef Ho D, Imai K, King G, Stuart E. MatchIt: non parametric processing for parametric causal inference. J Stat Software. 2011;42(8):1–28.CrossRef
18.
Zurück zum Zitat Kim SW. Korean hereditary breast cancer. JKMA. 2009;52:952–62. Kim SW. Korean hereditary breast cancer. JKMA. 2009;52:952–62.
19.
Zurück zum Zitat Peshkin BN, Alabek ML, Isaacs C. BRCA1/2 mutations and triple-negative breast cancers. Breast Dis. 2010;32:25–33.CrossRefPubMed Peshkin BN, Alabek ML, Isaacs C. BRCA1/2 mutations and triple-negative breast cancers. Breast Dis. 2010;32:25–33.CrossRefPubMed
20.
Zurück zum Zitat Pohl-Rescigno E, Hauke J, Loibl S, et al. Association of germline variant status with therapy response in high-risk early-stage breast cancer: a secondary analysis of the GeparOcto randomized clinical trial. JAMA Oncol. 2020;6:744–8.CrossRefPubMed Pohl-Rescigno E, Hauke J, Loibl S, et al. Association of germline variant status with therapy response in high-risk early-stage breast cancer: a secondary analysis of the GeparOcto randomized clinical trial. JAMA Oncol. 2020;6:744–8.CrossRefPubMed
21.
Zurück zum Zitat Ades F, Zardavas D, Bozovic-Spasojevic I, et al. Luminal B breast cancer: molecular characterization, clinical management, and future perspectives. J Clin Oncol. 2014;32:2794–803.CrossRefPubMed Ades F, Zardavas D, Bozovic-Spasojevic I, et al. Luminal B breast cancer: molecular characterization, clinical management, and future perspectives. J Clin Oncol. 2014;32:2794–803.CrossRefPubMed
22.
Zurück zum Zitat Criscitiello C, Curigliano G, Burstein HJ, et al. Breast conservation following neoadjuvant therapy for breast cancer in the modern era: are we losing the opportunity? Eur J Surg Oncol. 2016;42:1780–6.CrossRefPubMed Criscitiello C, Curigliano G, Burstein HJ, et al. Breast conservation following neoadjuvant therapy for breast cancer in the modern era: are we losing the opportunity? Eur J Surg Oncol. 2016;42:1780–6.CrossRefPubMed
23.
Zurück zum Zitat Geyer CE Jr, Garber JE, Gelber RD, et al. Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer. Ann Oncol. 2022;33:1250–68.CrossRefPubMed Geyer CE Jr, Garber JE, Gelber RD, et al. Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer. Ann Oncol. 2022;33:1250–68.CrossRefPubMed
Metadaten
Titel
Mutational Status is Associated with a Higher Rate of Pathologic Complete Response After Neoadjuvant Chemotherapy in Hormone Receptor-Positive Breast Cancer
verfasst von
Sara P. Myers, MD, PhD
Varadan Sevilimedu, MBBS, DrPH
Andrea V. Barrio, MD
Audree B. Tadros, MD
Anita Mamtani, MD
Mark E. Robson, MD
Monica Morrow, MD
Minna K. Lee, MD
Publikationsdatum
05.10.2023
Verlag
Springer International Publishing
Erschienen in
Annals of Surgical Oncology / Ausgabe 13/2023
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-023-14319-0

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