Double heterozygosity for BRCA1 and BRCA2 in breast cancer - considerations in surveillance and cancer risk management

Sep 23, 2026

Uploaded by Jake

This case report evaluates a premenopausal woman in her 30s with double heterozygosity (DH) for BRCA1 and BRCA2. Family cascade testing identified additional carriers among her relatives, underscoring the role of genetic counselling and family-wide surveillance. Given the rarity of DH, cancer risk estimates and optimal surveillance approaches are not addressed by existing guidelines, prompting a focused review of available evidence. The report compiles current literature and calls for further research to guide individualized cancer risk management.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages5

Reading Time13 min

AccessFree to download

Summary

Background

Case Presentation

Investigations

Differential Diagnosis

Treatment

Outcome and Follow-up

Case report Double heterozygosity for BRCA1 and BRCA2 in breast cancer: considerations in surveillance and cancer risk management Nonoko Wakaki , 1 Tatsunori Shimoi,2 Shogo Nakamoto,3 Yuichiro Kikawa,4 Aki Ito, 1 Takayuki Iwamoto5 1Breast Surgery, Japanese Red Cross Akita Hospital, Akita, Japan 2Medical Oncology, National Cancer Center Hospital, Chuoku, Tokyo, Japan 3Okayama University Hospital, Okayama, Japan 4Breast Surgery, Kansai Medical University Hirakata Hospital, Hirakata, Osaka, Japan 5Breast and Thyroid Surgery, Kawasaki Medical School Hospital, Kurashiki, Okayama, Japan Correspondence to Dr Nonoko Wakaki; [zozouo.uon.624@gmail.com](zozouo.uon.624@gmail.com) Accepted 7 April 2025 © BMJ Publishing Group Limited 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group. To cite: Wakaki N, Shimoi T, Nakamoto S, et al. BMJ Case Rep 2025;18:e263687 . doi:10 . 1136/bcr-2024- 263687 SUMMARY This case report examines a premenopausal woman in her 30s with double heterozygosity (DH) for BRCA1 and BRCA2 . The patient’s DH led her parents to undergo genetic testing as well, and new carriers were found, highlighting the importance of genetic counselling and surveillance for the entire family. Due to the rarity of DH, cancer risk and optimal surveillance strategies are not addressed in current guidelines or other sources. This report summarises existing evidence and highlights the need for further research to better understand cancer risks and to develop effective management strategies for individuals with this unique genetic profile. BACKGROUND Breast cancer is a significant malignancy affecting women globally. Approximately 6–10% of patients carry pathogenic variants indicative of hereditary breast cancer, most frequently in the BRCA1 and BRCA2 genes.1 2 These genetic alterations significantly increase the risk of breast cancer and other malignancies. Double heterozygosity (DH) in BRCA1 and BRCA2 is rare, and cancer risks and surveillance strategies for patients with DH remain poorly understood.3 4 This case report presents a patient with breast cancer who was found to have DH in BRCA1 and BRCA2 and includes a review of the literature on cancer risks and surveillance strategies. CASE PRESENTATION A premenopausal woman in her 30s presented with a palpable mass in her right breast. She had Hashimoto’s disease but no history of malignancies. She hada partner, no history of pregnancy or childbirth, and was considering infertility treatment. Physical examination revealed a palpable induration in the right breast. Her family history included multiple malignancies (figure 1). The patient’s mother had breast cancer and was undergoing treatment for ureteral and peritoneal cancer. Her maternal aunt had lactation-associated breast cancer, her paternal aunt had bilateral breast cancer, and her maternal grandfather died of pancreatic cancer. Additionally, several members of her maternal family had been diagnosed with leukaemia. INVESTIGATIONS Mammography identified a high-density, irregular mass in the right breast. Ultrasound revealed a lobulated, low-echoic, hypervascular mass in the right lower outer quadrant of the breast. Strain elastography showed decreased strain in this mass. MRI showed a mass with an irregular shape, indistinct margins and heterogeneity with rapid washout kinetics (figure 2). Based on these findings, the imaging results suggested breast cancer. CT and bone scintigraphy revealed no distant metastasis. Vacuum-assisted biopsy (VAB) confirmed the presence of an invasive ductal carcinoma. The preoperative diagnosis was right breast cancer, staged as T1cN0M0, Stage IA, according to the Union for International Cancer Control tumour–node–metastasis classification (eighth edition). DIFFERENTIAL DIAGNOSIS In this case, the diagnosis of breast cancer was established through standard clinical procedures, ultimately leading to su

FAQs

What is double heterozygosity for BRCA1 and BRCA2 in this case?

The patient was found to carry double heterozygous mutations in both BRCA1 and BRCA2. This genetic profile is described as rare, and its implications for cancer risk and surveillance are not well covered in current guidelines.

How was breast cancer diagnosed and staged?

Imaging showed a suspicious right breast mass, and vacuum-assisted biopsy confirmed invasive ductal carcinoma. The preoperative diagnosis was right breast cancer staged as T1cN0M0, Stage IA.

What follow-up and risk-management actions were taken after BRCA testing?

The patient received treatment and underwent genetic counselling during chemotherapy. BRCA analysis found an additional carrier in her mother, supporting family cascade testing and the need for surveillance and management across relatives.

Sep 23, 2026

Uploaded by Jake