Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2014

01-04-2014 | Review

Surgical management of breast cancer in BRCA-mutation carriers: a systematic review and meta-analysis

Authors: Antonis Valachis, Andreas D. Nearchou, Pehr Lind

Published in: Breast Cancer Research and Treatment | Issue 3/2014

Login to get access

Abstract

This meta-analysis investigates the oncological safety of breast-conserving therapy BCT in BRCA-mutation carriers and the risk for contralateral breast cancer (CBC) compared with non-carriers, potential risk factors for ipsilateral breast recurrence (IBR) or CBC and grades these factors based on the level of evidence. A PubMed search was conducted through April 2013 to identify studies that described the risk for IBR and CBC after BCT in BRCA-mutation carriers versus non-carriers as well as studies that investigated risk factors for IBR and CBC in BRCA-mutation carriers. Results were summarized using meta-analysis when sufficient studies were available. Ten studies investigated the oncological safety of BCT in BRCA-mutation carriers versus non-carriers. There was no significant difference in IBR between carriers and controls (RR 1.45, 95 % CI 0.98–2.14). However, a significant higher risk for IBR in BRCA-mutation carriers was observed in studies with a median follow-up ≥7 years (RR 1.51, 95 % CI 1.15–1.98). CBCs were significantly greater in carriers versus controls (RR 3.56, 95 % CI 2.50–5.08). Use of adjuvant chemotherapy and oophorectomy were associated with a significantly lower risk for IBR in BRCA-mutation carriers. Three factors were associated with a lower risk for CBC in BRCA-mutation carriers: oophorectomy, use of tamoxifen, and age at first breast cancer. Based on current evidence, the use of BCT in BRCA-mutation carriers can be considered a reasonable option since it does not seem to increase the risk for IBR. However, several aspects should be taken into account before the final decision-making.
Appendix
Available only for authorised users
Literature
1.
2.
3.
Clarke M, Collins R, Darby S, Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) et al (2005) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366:2087–2106PubMedCrossRef
4.
Brekelmans CT, Tilanus-Linthorst MM, Seynaeve C et al (2007) Tumour characteristics, survival and prognostic factors of hereditary breast cancer from BRCA2-, BRCA1- and non-BRCA1/2 families as compared to sporadic breast cancer cases. Eur J Cancer 43:867–876PubMedCrossRef
5.
Chappuis PO, Kapusta L, Bégin LR et al (2000) Germline BRCA1/2 mutations and p27(Kip1) protein levels independently predict outcome after breast cancer. J Clin Oncol 18:4045–4052PubMed
6.
Eccles D, Simmonds P, Goddard J et al (2001) Familial breast cancer: an investigation into the outcome of treatment for early stage disease. Fam Cancer 1:65–72PubMedCrossRef
7.
El-Tamer M, Russo D, Troxel A et al (2004) Survival and recurrence after breast cancer in BRCA1/2 mutation carriers. Ann Surg Oncol 11:157–164PubMedCrossRef
8.
Garcia-Etienne CA, Barile M, Gentilini OD et al (2009) Breast-conserving surgery in BRCA1/2 mutation carriers: are we approaching an answer? Ann Surg Oncol 16:3380–3387PubMedCrossRef
9.
Haffty BG, Harrold E, Khan AJ et al (2002) Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status. Lancet 359:1471–1477PubMedCrossRef
10.
Kirova YM, Savignoni A, Sigal-Zafrani B et al (2010) Is the breast-conserving treatment with radiotherapy appropriate in BRCA1/2 mutation carriers? Long-term results and review of the literature. Breast Cancer Res Treat 120:119–126PubMedCrossRef
11.
Metcalfe K, Gershman S, Lynch HT et al (2011) Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. Br J Cancer 104:1384–1392PubMedCentralPubMedCrossRef
12.
Metcalfe K, Lynch HT, Ghadirian P et al (2011) Risk of ipsilateral breast cancer in BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat 127:287–296PubMedCrossRef
13.
Pierce LJ, Phillips KA, Griffith KA et al (2010) Local therapy in BRCA1 and BRCA2 mutation carriers with operable breast cancer: comparison of breast conservation and mastectomy. Breast Cancer Res Treat 121:389–398PubMedCentralPubMedCrossRef
14.
Pierce LJ, Levin AM, Rebbeck TR et al (2006) Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol 24:2437–2443PubMedCrossRef
15.
Robson ME, Chappuis PO, Satagopan J et al (2004) A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment. Breast Cancer Res 6:R8–R17PubMedCentralPubMedCrossRef
16.
Stoppa-Lyonnet D, Ansquer Y, Dreyfus H et al (2000) Familial invasive breast cancers: worse outcome related to BRCA1 mutations. J Clin Oncol 18:4053–4059PubMed
17.
Stroup DF, Berlin JA, Morton SC et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA 283:2008–2012PubMedCrossRef
18.
Viswanathan M, Berkman ND (2012) Development of the RTI item bank on risk of bias and precision of observational studies. J Clin Epidemiol 65:163–178PubMedCrossRef
19.
Huang E, Buchholz TA, Meric F et al (2002) Classifying local disease recurrences after breast conservation therapy based on location and histology: new primary tumors have more favorable outcomes than true local disease recurrences. Cancer 95:2059–2067PubMedCrossRef
20.
Panet-Raymond V, Truong PT, McDonald RE, Alexander C, Ross L, Ryhorchuk A, Watson PH (2011) True recurrence versus new primary: an analysis of ipsilateral breast tumor recurrences after breast-conserving therapy. Int J Radiat Oncol Biol Phys 81:409–417PubMedCrossRef
21.
Smith TE, Lee D, Turner BC, Carter D, Haffty BG (2000) True recurrence vs. new primary ipsilateral breast tumor relapse: an analysis of clinical and pathologic differences and their implications in natural history, prognoses, and therapeutic management. Int J Radiat Oncol Biol Phys 48:1281–1289PubMedCrossRef
22.
Pierce LJ, Strawderman M, Narod SA et al (2000) Effect of radiotherapy after breast-conserving treatment in women with breast cancer and germline BRCA1/2 mutations. J Clin Oncol 18:3360–3369PubMed
23.
Robson M, Gilewski T, Haas B et al (1998) BRCA-associated breast cancer in young women. J Clin Oncol 16:1642–1649PubMed
24.
Graeser MK, Engel C, Rhiem K et al (2009) Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 27:5887–5892PubMedCrossRef
25.
Mavaddat N, Peock S, Frost D, on behalf of EMBRACE et al (2013) Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. J Natl Cancer Inst 105:812–822PubMedCrossRef
26.
Robson M, Svahn T, McCormick B, Borgen P, Hudis CA, Norton L, Offit K (2005) Appropriateness of breast-conserving treatment of breast carcinoma in women with germline mutations in BRCA1 or BRCA2: a clinic-based series. Cancer 103:44–51PubMedCrossRef
27.
van der Kolk DM, de Bock GH, Leegte BK, Schaapveld M, Mourits MJ, de Vries J, van der Hout AH, Oosterwijk JC (2010) Penetrance of breast cancer, ovarian cancer and contralateral breast cancer in BRCA1 and BRCA2 families: high cancer incidence at older age. Breast Cancer Res Treat 124:643–651PubMedCrossRef
28.
Gronwald J, Tung N, Foulkes WD, Hereditary Breast Cancer Clinical Study Group et al (2006) Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. Int J Cancer 118:2281–2284PubMedCrossRef
29.
Malone KE, Begg CB, Haile RW et al (2010) Population-based study of the risk of second primary contralateral breast cancer associated with carrying a mutation in BRCA1 or BRCA2. J Clin Oncol 28:2404–2410PubMedCentralPubMedCrossRef
30.
Reding KW, Bernstein JL, Langholz BM, WECARE Collaborative Study Group (2010) Adjuvant systemic therapy for breast cancer in BRCA1/BRCA2 mutation carriers in a population-based study of risk of contralateral breast cancer. Breast Cancer Res Treat 123:491–498PubMedCentralPubMedCrossRef
31.
Verhoog LC, Brekelmans CT, Seynaeve C, Meijers-Heijboer EJ, Klijn JG (2000) Contralateral breast cancer risk is influenced by the age at onset in BRCA1-associated breast cancer. Br J Cancer 83:384–386PubMedCentralPubMedCrossRef
32.
van Sprundel TC, Schmidt MK, Rookus MA, Brohet R, van Asperen CJ, Rutgers EJ, Van’t Veer LJ, Tollenaar RA (2005) Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers. Br J Cancer 93:287–292PubMedCentralPubMedCrossRef
33.
Goodwin PJ, Phillips KA, West DW et al (2012) Breast cancer prognosis in BRCA1 and BRCA2 mutation carriers: an international prospective breast cancer family registry population-based cohort study. J Clin Oncol 30:19–26PubMedCrossRef
34.
Rennert G, Bisland-Naggan S, Barnett-Griness O, Bar-Joseph N, Zhang S, Rennert HS, Narod SA (2007) Clinical outcomes of breast cancer in carriers of BRCA1 and BRCA2 mutations. N Engl J Med 357:115–123PubMedCrossRef
35.
Lostumbo L, Carbine NE, Wallace J (2010) Prophylactic mastectomy for the prevention of breast cancer. Cochrane Database Syst Rev 11:CD002748PubMed
36.
Heemskerk-Gerritsen B, Hooning M, van Asperen CJ et al (2013) Efficacy of risk-reducing mastectomy (RRM) on overall survival (OS) in BRCA1/2-associated breast cancer (BC) patients. J Clin Oncol (Meeting Abstracts) 31(15 suppl):1502
37.
Fourquet A, Stoppa-Lyonnet D, Kirova YM, Sigal-Zafrani B, Asselain B, Institut Curie Breast Cancer Study Group, Institut Curie Breast Ovary Cancer Risk Study Group (2009) Familial breast cancer: clinical response to induction chemotherapy or radiotherapy related to BRCA1/2 mutations status. Am J Clin Oncol 32:127–131PubMedCrossRef
38.
Kriege M, Seynaeve C, Meijers-Heijboer H et al (2009) Sensitivity to first-line chemotherapy for metastatic breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 27:3764–3771PubMedCrossRef
39.
Brandberg Y, Sandelin K, Erikson S et al (2008) Psychological reactions, quality of life, and body image after bilateral prophylactic mastectomy in women at high risk for breast cancer: a prospective 1-year follow-up study. J Clin Oncol 26:3943–3949PubMedCrossRef
40.
Tercyak KP, Peshkin BN, Brogan BM et al (2007) Quality of life after contralateral prophylactic mastectomy in newly diagnosed high-risk breast cancer patients who underwent BRCA1/2 gene testing. J Clin Oncol 25:285–291PubMedCrossRef
41.
Unukovych D, Sandelin K, Liljegren A, Arver B, Wickman M, Johansson H, Brandberg Y (2012) Contralateral prophylactic mastectomy in breast cancer patients with a family history: a prospective 2-years follow-up study of health related quality of life, sexuality and body image. Eur J Cancer 48:3150–3156PubMedCrossRef
42.
Frost MH, Slezak JM, Tran NV et al (2005) Satisfaction after contralateral prophylactic mastectomy: the significance of mastectomy type, reconstructive complications, and body appearance. J Clin Oncol 23:7849–7856PubMedCrossRef
43.
Da Silva L, Lakhani SR (2010) Pathology of hereditary breast cancer. Mod Pathol Suppl 2:S46–S51CrossRef
44.
Rebbeck TR, Kauff ND, Domchek SM (2009) Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst 101:80–87PubMedCentralPubMedCrossRef
Metadata
Title
Surgical management of breast cancer in BRCA-mutation carriers: a systematic review and meta-analysis
Authors
Antonis Valachis
Andreas D. Nearchou
Pehr Lind
Publication date
01-04-2014
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2014
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-014-2890-1

Other articles of this Issue 3/2014

Breast Cancer Research and Treatment 3/2014 Go to the issue

Preclinical Study

Primary breast tumor-derived cellular models: characterization of tumorigenic, metastatic, and cancer-associated fibroblasts in dissociated tumor (DT) cultures

Clinical Trial

Germline variants in the CYP19A1 gene are related to specific adverse events in aromatase inhibitor users: a substudy of Dutch patients in the TEAM trial

Epidemiology

Recurrent mutation testing of BRCA1 and BRCA2 in Asian breast cancer patients identify carriers in those with presumed low risk by family history

Clinical trial

31P magnetic resonance spectroscopy of the breast and the influence of the menstrual cycle

Preclinical study

Combined analysis of gene expression, DNA copy number, and mutation profiling data to display biological process anomalies in individual breast cancers

Clinical trial

A phase II, multicentre trial evaluating the efficacy of de-escalated bisphosphonate therapy in metastatic breast cancer patients at low-risk of skeletal-related events
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

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
Image Credits