Case report: metachronous male metastatic breast and colon cancer in a BRCA2 mutation carrier

Abstract

Introduction and Importance

Male breast cancer (MBC) is rare and typically diagnosed at later stages, often in older men. Pathogenic BRCA2 mutations are implicated in a significant proportion of MBC cases and may confer increased risk for other cancers.

Case presentation

A 66-year-old male presented with right upper limb edema and back soreness. Imaging and biopsy confirmed stage IV invasive ductal carcinoma, Luminal B HER2-negative. Genetic testing revealed a germline BRCA2 mutation. During routine imaging, a second primary colon cancer was discovered and resected.

Clinical discussion

MBC represents less than 1% of all male cancers and is frequently associated with delayed diagnosis. BRCA2 mutations significantly increase the risk for male breast and gastrointestinal cancers. This patient underwent endocrine and CDK4/6 inhibitor therapy and followed by surgery and adjuvant chemotherapy for the colon carcinoma. Disease remained stable on follow-up.

Conclusion

This case highlights the importance of genetic testing, vigilance for second primary malignancies in BRCA2 carriers, and the value of multidisciplinary care for MBC patients. The co-occurrence of these malignancies in a male BRCA2 carrier is rare and underscores the need for broader surveillance in such patients.

Introduction

Male breast cancer (MBC) accounts for less than 1% of all male cancers [1]. It typically presents at a later stage, with many cases diagnosed as invasive ductal carcinoma. MBC is frequently hormone receptor-positive. Treatment guidelines are often extrapolated from female breast cancer (FBC) due to its rarity. Germline BRCA2 mutations, implicated in 12.5% of MBC cases, also increase the risk for prostate, pancreatic, and colorectal cancers [2, 3]. The concomitant presentation at initial diagnosis of metastatic breast cancer and a colon cancer to a patient who harbor a germline BRCA mutation is a unique feature as, it is known the male patients with BRCA mutations are more at risk for developing prostate or pancreatic cancer. This case is particularly noteworthy due to the unusual combination of male metastatic breast cancer and a metachronous colon carcinoma in a BRCA2 mutation carrier, a pattern not commonly observed.

Patient information

A 66-year-old Caucasian male with a history of alcoholic cardiomyopathy presented with progressive right upper limb edema and right upper back soreness over several weeks. Family history was significant for breast cancer in two sisters and two brothers, and both parents died of unspecified cancers.

Clinical findings

Clinical evaluation revealed right retroareolar swelling with skin retraction. CT imaging confirmed a retroareolar mass (18 mm) with associated right axillary and supraclavicular lymphadenopathy (Fig. 1). Mammography showed an irregular retro‑areolar mass with microcalcifications and associated right axillary adenopathy (Fig. 2). Breast ultrasound showed an irregular hypoechoic mass (20 × 12 × 2 mm) with microcalcifications and skin thickening. Multiple right axillary lymph nodes were enlarged with capsular rupture.

Fig. 1.

Contrast‑enhanced CT images of the right breast and axilla showing a retro‑areolar lesion (18 mm) and right axillary/supraclavicular lymphadenopathy

Fig. 2.

Mammography (mediolateral oblique view) demonstrating an irregular retro‑areolar mass with microcalcifications and associated right axillary adenopathy

Timeline

• Initial presentation: right arm edema and soreness.

• Diagnosis: stage IV invasive ductal carcinoma.

• Initiation of endocrine therapy and abemaciclib.

• 3-month imaging: stable breast disease, discovery of colon lesion.

• Surgery: laparoscopic colectomy.

• Follow-up: stable disease, abemaciclib discontinued.

Diagnostic assessment

Biopsy confirmed invasive ductal carcinoma, grade III, Luminal B HER2-negative (ER+, PR+, HER2 2+, Ki67 25%). Axillary FNA showed metastatic carcinoma. Bone scan and MRI revealed osseous metastases, (ribs, vertebrae) (Fig. 3). Genetic testing confirmed a germline BRCA2 mutation. Later CT and colonoscopy revealed a left-sided colonic mass (Fig. 4); biopsy showed moderately differentiated adenocarcinoma. Post-resection pathology showed pT4aN2b, medullary features, MMR proficient. DPD activity was normal. Specifically, a heterozygote status of a pathogenic germline BRCA2 variant (c.6275_6276del p. (Leu2092Profs*7)) was identified via next-generation sequencing (NGS).

Fig. 3.

Sagittal spine MRI illustrating a vertebral body lesion consistent with bone metastasis

Fig. 4.

Contrast-enhanced CT scan showing a left-sided colonic mass (3.2 cm) suspicious for adenocarcinoma

Therapeutic interventions

Initial treatment included goserelin, letrozole, abemaciclib, and denosumab. Ribociclib was contraindicated due to arrhythmia. Colon resection was performed after pausing abemaciclib perioperatively. Due to the BRCA2 mutation and high-risk colon cancer features, adjuvant chemotherapy with simplified FOLFOX4 was initiated. Abemaciclib was discontinued after 6 months, during chemotherapy, to prevent a hematologic toxicity. Hormonotherapy was continued.

Follow-up and outcomes

Three- and six-month evaluations showed stable disease on CT and bone scan. Bone consolidation was noted. The patient had occasional grade 1 diarrhea and fatigue but maintained good general condition and adherence to treatment.

Discussion

This case illustrates the complexity of managing MBC in a BRCA2 mutation carrier, particularly when complicated by metachronous colon cancer. BRCA mutations increase the risk of developing other cancer such as prostate cancer and pancreatic cancer. The association of breast cancer and colon cancer in a male patient harbor a germline mutation is unusual. BRCA2 mutations predispose patients to a spectrum of malignancies and has been associated with increased cancer risks but treatment sensitivity was not evaluated in this case [2, 3]. Early genetic testing informed treatment planning, surveillance, and family counseling. This case supports the importance of a multidisciplinary approach to BRCA-mutated MBC patients. Early genetic testing in this case enabled personalized treatment and informed surveillance [4, 5]. The patient and family members underwent genetic counseling, highlighting the importance of cascade testing. Therapeutic management incorporated endocrine therapy and CDK4/6 inhibitors followed by adjuvant chemotherapy for colon cancer, demonstrating the necessity of coordinated multidisciplinary care.

Patient perspective

The patient expressed relief at having a diagnosis and appreciated the personalized care. He was motivated to ensure his daughter was tested for the BRCA2 mutation.

Author contributions

E-V.L. wrote the main manuscript; O-N. P. prepared the Figs. 1, 2, 3, 4 and 5 and C.S. proofread the manuscript; All authors reviewed the manuscript.

Funding

This work received no specific funding from public, commercial, or not-for-profit agencies.

Data availability

All data generated or analyzed during this study are included in this published article.

Declarations

Ethics approval and consent to participate

Ethical approval was not required for this case report in accordance with Belgian national regulations and institutional policies. The need for ethical approval was waived by the Comité d’éthique of the Centre Hospitalier de Wallonie Picarde (CHwapi). The study was conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent to participate in this study was obtained from the patient.

Consent for publication

Written informed consent for publication of this case report and any accompanying images was obtained from the patient.

Competing interests

The authors declare no competing interests.