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Identification of a new BRCA2 large genomic deletion associated with high risk male breast cancer.

Timoteo AR, Albuquerque BM, Moura PC, Ramos CC, Agnez-Lima LF, Walsh T, King MC, Lajus TB - Hered Cancer Clin Pract (2015)

Bottom Line: Large rearrangements in BRCA1 and BRCA2 occur in a small percentage (<1%) of patients tested for hereditary breast and ovarian cancer.Mutation segregation analysis should be further done in the Brazilian population.Herein we highlight the importance of next-generation sequencing in the detection of large genomic deletions.

View Article: PubMed Central - PubMed

Affiliation: Universidade Federal do Rio Grande do Norte, Av. Senador Salgado Filho, s/n, Natal, RN Brazil.

ABSTRACT

Background: Male breast cancer (MBC) is an uncommon disease that has been the focus of limited research. It is estimated that approximately 10% of men with breast cancer have a genetic predisposition, with BRCA2 being the most prevalent genetic mutation. Here we describe the case of MBC in a 64-year-old man who presented on physical examination a nodule in his left breast and declared to have an extensive family history of cancer.

Methods and results: The patient was firstly diagnosed with an invasive ductal carcinoma (IDC) with histological grade III, nuclear grade 3, pT4N2Mx and positive for hormonal receptors and HER2. Exome sequencing was performed by massive parallel sequencing which had detected a novel BRCA2 germline mutation that is a large genomic deletion of 3,492 nucleotides including BRCA2 exon 14, and this deletion is out of frame and is predicted to lead to a stop codon in exon 15 at codon 2,496.

Conclusion: Large rearrangements in BRCA1 and BRCA2 occur in a small percentage (<1%) of patients tested for hereditary breast and ovarian cancer. This is the first report of the mutation del3492 in BRCA2 exon 14, which leads to a truncated protein and therefore is clinically relevant. Mutation segregation analysis should be further done in the Brazilian population. Herein we highlight the importance of next-generation sequencing in the detection of large genomic deletions.

No MeSH data available.


Related in: MedlinePlus

Patient pedigree. II.3 is the proband (indicated by an arrow). The figure shows a family history of cancer of 2 generations. Father dead of prostate cancer (I.1). Mother and sisters dead of breast cancer (I.2, II.6, II.7, II.8, II.10, II.11, II.12, respectively) and four brothers dead of unknown cancer (II.1, 2, 4, 5). Two daughters from first marriage also have been diagnosed with breast cancer (III.1 and III.2). The age of diagnostic are indicated (Dx).
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Fig1: Patient pedigree. II.3 is the proband (indicated by an arrow). The figure shows a family history of cancer of 2 generations. Father dead of prostate cancer (I.1). Mother and sisters dead of breast cancer (I.2, II.6, II.7, II.8, II.10, II.11, II.12, respectively) and four brothers dead of unknown cancer (II.1, 2, 4, 5). Two daughters from first marriage also have been diagnosed with breast cancer (III.1 and III.2). The age of diagnostic are indicated (Dx).

Mentions: A 64 year-old man reported a painful node in the left breast since 2 years (2008). He related a strong familial breast cancer history (father dead - prostate cancer, mother and six sisters dead - breast cancer, four out of five brothers dead – cancer not identified) (Figure 1). He denied using drugs or anabolic steroids and did not drink large amounts of alcohol. On physical examination, an irregular sub areolar node was detected. Although gynecomastia has been suggested to be present in 6-38% of breast cancer cases in men, it was not evident in our patient [11]. The nipple was not retracted and the left axillary lymphnodes were palpable. The right breast was normal. On sonography a node measuring 3.4 cm with BI-RADS score 4 was detected. After core biopsy, the material was sent for a frozen section (0.6 × 0.5 × 0.6 cm). The diagnosis was invasive ductal carcinoma (IDC) with histological grade III and nuclear grade 3 (Figure 2). The patient did not present himself to the hospital during 1 year. After 1 year, the patient returned to the Medical Service and was submitted to a left radical mastectomy and axillary dissection. Histology confirmed an IDC of 2.5 cm, grade 3 and six out of 23 lymph nodes were positive, staging resulted in pT4N2Mx (tumor, node and metastatic involvement). Tumor size and lymph node involvement are two clear prognostic factors for male patients with breast cancer. Men with tumors measuring 2–5 cm have a 40% higher risk of death than men with tumors <2 cm in maximum diameter. Immunohistochemical analysis showed that the tumor was positive for the presence of estrogen/progesterone receptors and for the human epidermal growth factor receptor-2 (HER-2). The patient initiated adjuvant treatment with 4 cycles of TAC (Taxotere, Adriamycin and Cyclophosphamide). Following adjuvant treatment he was treated with local radiotherapy, dose 5.000 cGy (25 × 200 cGy), followed by a treatment with tamoxifen from 2010 until the present (35 months). The bone scintigraphy showed other pathologic sites at T9, L1, ischium and acetabulum (Figure 3), therefore treatment was associated with pamidronate.Figure 1


Identification of a new BRCA2 large genomic deletion associated with high risk male breast cancer.

Timoteo AR, Albuquerque BM, Moura PC, Ramos CC, Agnez-Lima LF, Walsh T, King MC, Lajus TB - Hered Cancer Clin Pract (2015)

Patient pedigree. II.3 is the proband (indicated by an arrow). The figure shows a family history of cancer of 2 generations. Father dead of prostate cancer (I.1). Mother and sisters dead of breast cancer (I.2, II.6, II.7, II.8, II.10, II.11, II.12, respectively) and four brothers dead of unknown cancer (II.1, 2, 4, 5). Two daughters from first marriage also have been diagnosed with breast cancer (III.1 and III.2). The age of diagnostic are indicated (Dx).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4308828&req=5

Fig1: Patient pedigree. II.3 is the proband (indicated by an arrow). The figure shows a family history of cancer of 2 generations. Father dead of prostate cancer (I.1). Mother and sisters dead of breast cancer (I.2, II.6, II.7, II.8, II.10, II.11, II.12, respectively) and four brothers dead of unknown cancer (II.1, 2, 4, 5). Two daughters from first marriage also have been diagnosed with breast cancer (III.1 and III.2). The age of diagnostic are indicated (Dx).
Mentions: A 64 year-old man reported a painful node in the left breast since 2 years (2008). He related a strong familial breast cancer history (father dead - prostate cancer, mother and six sisters dead - breast cancer, four out of five brothers dead – cancer not identified) (Figure 1). He denied using drugs or anabolic steroids and did not drink large amounts of alcohol. On physical examination, an irregular sub areolar node was detected. Although gynecomastia has been suggested to be present in 6-38% of breast cancer cases in men, it was not evident in our patient [11]. The nipple was not retracted and the left axillary lymphnodes were palpable. The right breast was normal. On sonography a node measuring 3.4 cm with BI-RADS score 4 was detected. After core biopsy, the material was sent for a frozen section (0.6 × 0.5 × 0.6 cm). The diagnosis was invasive ductal carcinoma (IDC) with histological grade III and nuclear grade 3 (Figure 2). The patient did not present himself to the hospital during 1 year. After 1 year, the patient returned to the Medical Service and was submitted to a left radical mastectomy and axillary dissection. Histology confirmed an IDC of 2.5 cm, grade 3 and six out of 23 lymph nodes were positive, staging resulted in pT4N2Mx (tumor, node and metastatic involvement). Tumor size and lymph node involvement are two clear prognostic factors for male patients with breast cancer. Men with tumors measuring 2–5 cm have a 40% higher risk of death than men with tumors <2 cm in maximum diameter. Immunohistochemical analysis showed that the tumor was positive for the presence of estrogen/progesterone receptors and for the human epidermal growth factor receptor-2 (HER-2). The patient initiated adjuvant treatment with 4 cycles of TAC (Taxotere, Adriamycin and Cyclophosphamide). Following adjuvant treatment he was treated with local radiotherapy, dose 5.000 cGy (25 × 200 cGy), followed by a treatment with tamoxifen from 2010 until the present (35 months). The bone scintigraphy showed other pathologic sites at T9, L1, ischium and acetabulum (Figure 3), therefore treatment was associated with pamidronate.Figure 1

Bottom Line: Large rearrangements in BRCA1 and BRCA2 occur in a small percentage (<1%) of patients tested for hereditary breast and ovarian cancer.Mutation segregation analysis should be further done in the Brazilian population.Herein we highlight the importance of next-generation sequencing in the detection of large genomic deletions.

View Article: PubMed Central - PubMed

Affiliation: Universidade Federal do Rio Grande do Norte, Av. Senador Salgado Filho, s/n, Natal, RN Brazil.

ABSTRACT

Background: Male breast cancer (MBC) is an uncommon disease that has been the focus of limited research. It is estimated that approximately 10% of men with breast cancer have a genetic predisposition, with BRCA2 being the most prevalent genetic mutation. Here we describe the case of MBC in a 64-year-old man who presented on physical examination a nodule in his left breast and declared to have an extensive family history of cancer.

Methods and results: The patient was firstly diagnosed with an invasive ductal carcinoma (IDC) with histological grade III, nuclear grade 3, pT4N2Mx and positive for hormonal receptors and HER2. Exome sequencing was performed by massive parallel sequencing which had detected a novel BRCA2 germline mutation that is a large genomic deletion of 3,492 nucleotides including BRCA2 exon 14, and this deletion is out of frame and is predicted to lead to a stop codon in exon 15 at codon 2,496.

Conclusion: Large rearrangements in BRCA1 and BRCA2 occur in a small percentage (<1%) of patients tested for hereditary breast and ovarian cancer. This is the first report of the mutation del3492 in BRCA2 exon 14, which leads to a truncated protein and therefore is clinically relevant. Mutation segregation analysis should be further done in the Brazilian population. Herein we highlight the importance of next-generation sequencing in the detection of large genomic deletions.

No MeSH data available.


Related in: MedlinePlus