J Breast Cancer.  2019 Dec;22(4):587-598. 10.4048/jbc.2019.22.e47.

Contralateral Breast Cancer and Ipsilateral Breast Tumor Recurrence in BRCA1/2 Carriers and Non-Carriers at High-Risk of Hereditary Breast Cancer

Affiliations
  • 1Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea. ekkim.md@gmail.com
  • 2Department of Surgery, Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul, Korea.
  • 3Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
  • 4Department of Radiation Oncology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
  • 5Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
  • 6Department of Surgery, Daerim St. Mary's Hospital, Seoul, Korea.

Abstract

PURPOSE
We evaluated the risk of contralateral breast cancer (CBC) and ipsilateral breast tumor recurrence (IBTR) and investigated the predictive factors for CBC and IBTR in breast cancer patients with BRCA mutations and non-carriers at high-risk of hereditary breast and ovarian cancer (HBOC).
METHODS
We analyzed prospectively collected clinical data of patients with unilateral breast cancer who were at high-risk for HBOC and were tested for the BRCA mutation between 2003 and 2013.
RESULTS
The cohort comprised 540 patients with 45 BRCA1 carriers, 50 BRCA2 carriers, and 445 non-carriers. The median follow-up was 84.5 months. Overall, 61 patients (11.3%) developed CBC (24.4% for BRCA1 carriers, 20% for BRCA2 carriers, and 9% for non-carriers). The 10-year cumulative risk for CBC was 23.8% for BRCA1 carriers, 19.1% for BRCA2 carriers, and 9.8% for non-carriers (p = 0.174). Among the 277 patients who underwent breast-conserving surgery, 29 (10.5%) developed IBTR (9.1% for BRCA1 carriers, 16.7% for BRCA2 carriers, and 10.2% for non-carriers). The 10-year cumulative risk for IBTR for BRCA1 carriers, BRCA2 carriers, and non-carriers was 8.7%, 14.1%, and 20%, respectively (p = 0.577). BRCA1 (hazard ratio [HR], 2.94; 95% confidence interval [CI], 1.20-7.20; p = 0.019) and BRCA2 (HR, 2.88; 95% CI, 1.13-7.35; p = 0.027) mutations and negative estrogen receptor status (HR, 4.02; 95% CI, 1.60-10.08; p = 0.003) were the significant predictive factors for CBC, while tumor size ≥ 2 cm was predictive of IBTR (HR, 6.11; 95% CI, 2.03-18.33; p = 0.001).
CONCLUSION
While BRCA1/2 mutation carriers had a higher risk of developing CBC compared to non-carriers at high-risk of HBOC, the risk of IBTR was similarly high across breast cancer patients irrespective of the BRCA mutation. Further preventive strategies to reduce CBC and IBTR for all patients at high-risk of HBOC should be investigated.

Keyword

Breast neoplasms; Genes, BRCA1; Genes, BRCA2; Hereditary breast and ovarian cancer syndrome; Risk factors

MeSH Terms

Breast Neoplasms*
Breast*
Cohort Studies
Estrogens
Follow-Up Studies
Genes, BRCA1
Genes, BRCA2
Hereditary Breast and Ovarian Cancer Syndrome
Humans
Mastectomy, Segmental
Ovarian Neoplasms
Prospective Studies
Recurrence*
Risk Factors
Unilateral Breast Neoplasms
Estrogens

Figure

  • Figure 1 Diagram for case enrollment. HBOC = hereditary breast and ovarian cancer; CBC = contralateral breast cancer; IBTR = ipsilateral breast tumor recurrence.

  • Figure 2 Cumulative risks of CBC. CBC = contralateral breast cancer.

  • Figure 3 Cumulative risks of IBTR. IBTR = ipsilateral breast tumor recurrence.


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