Germline molecular data in hereditary breast cancer in Brazil: Lessons from a large single-center analysis.

Brazil is the largest country in South America and the most genetically heterogeneous. The aim of the present study was to determine the prevalence of germline pathogenic variants (PVs) in Brazilian patients with breast cancer (BC) who underwent genetic counseling and genetic testing at a tertiary Oncology Center. We performed a retrospective analysis of the medical records of Brazilian patients with BC referred to genetic counseling and genetic testing between August 2017 and August 2019. A total of 224 unrelated patients were included in this study. Premenopausal women represented 68.7% of the cohort. The median age at BC diagnosis was 45 years. Multigene panel testing was performed in 219 patients, five patients performed single gene analysis or family variant testing. Forty-eight germline PVs distributed among 13 genes were detected in 20.5% of the patients (46/224). Eighty-five percent of the patients (91/224) fulfilled NCCN hereditary BC testing criteria. Among these patients, 23.5% harbored PVs (45/191). In the group of patients that did not meet NCCN criteria, PV detection rate was 3% (1/33). A total of 61% of the patients (28/46) harbored a PV in a high-penetrance BC gene: 19 (8.5%) BRCA1/2, 8 (3.5%) TP53, 1 (0.5%) PALB2. Moderate penetrance genes (ATM, CHEK2) represented 15.2% (7/46) of the positive results. PVs detection was statistically associated (p<0.05) with BC diagnosis before age 45, high-grade tumors, bilateral BC, history of multiple primary cancers, and family history of pancreatic cancer. According to the current hereditary cancer guidelines, 17.4% (39/224) of the patients had actionable variants. Nine percent of the patients (20/224) had actionable variants in non-BRCA genes, it represented 43.5% of the positive results and 51.2% of the actionable variants. Considering the observed prevalence of PVs in actionable genes beyond BRCA1/2 (9%, 20/224), multigene panel testing may offer an effective first-tier diagnostic approach in this population.

Novel Insights From the Germline Landscape of Breast Cancer in Brazil.

INTRODUCTION: Breast cancer patients with germline pathogenic variants may benefit from risk-reducing surgeries, intensive screening, and targeted cancer therapies. There is a paucity of data regarding prevalence and distribution of germline pathogenic variants in the Brazilian population. Our primary endpoint was the description of prevalence and distribution of germline pathogenic variants among breast cancer patients who underwent next-generation sequencing (NGS) panel testing. Secondary endpoint was the assessment of predictive factors of a positive test. METHODS: We analyzed NGS results, personal, and family history data from a prospectively collected cohort of breast cancer patients from August 2013 to May 2019. Exact logistic regression was used to perform multivariable analysis. RESULTS: Of 370 breast cancer patients, we found 59 pathogenic variants in 57 (15%) patients. Pathogenic variants were identified in BRCA1 (24%), ATM (14%), BRCA2 (10%), TP53 (8%), PALB2 (8%), CHEK2 (7%), CDH1 (3%), RAD51C (3%), MITF (2%), PMS2 (2%), RAD51D (2%), and TERT (2%). Monoallelic MUTYH pathogenic variants were found in 15%. After multivariable analysis, age of diagnosis (OR 0.89, 95% CI: 0.81-0.95, for each year increase), triple-negative subtype (OR 17.2, 95% CI: 3.74-114.72), and number of breast cancers in the family (OR 2.46, 95% CI 1.57-4.03, for each additional case) were associated with BRCA1 pathogenic variants. In the present study, a quarter of triple-negative breast cancer patients harbored a germline pathogenic variant and two-thirds of those were BRCA1 carriers. CONCLUSIONS: Prevalence and distribution of germline pathogenic variants in this Brazilian sample of breast cancer patients are mostly similar to other populations. However, there is a trend to an overrepresentation of TP53 pathogenic variants that merits confirmation in further studies. Early-onset breast cancer patients should be offered genetic counseling, particularly those with triple-negative subtype.

Necrotizing fasciitis of breast in postpartum period: case report / Fasciíte necrotizante de mama no puerpério: relato de caso

Necrotizing fasciitis is an aggressive infection that affects subcutaneous and superficial fascia by necrosis, more often found in the abdominal wall, perineum and extremities. Rare cases have been described in the breast and the literature points to breastfeeding and previous breast procedures as risk factors for this condition. We present a 27-year-old patient in postpartum period who presented a right nipple fissure associated to breastfeeding, that evolved to a local aggressive infection with extensive necrosis of fascia and mammary parenchyma characterized as necrotizing fasciitis. Our aim is to highlight the importance of early diagnosis, especially to differentiate from puerperal mastitis which has a different pathophysiology and treatment, as well as the need for appropriate therapy consisting of surgical debridement and broad spectrum antibiotics in order to avoid further complications and death

Fasciíte necrotizante é uma infecção agressiva que acomete o subcutâneo e fáscias superficiais por necrose, mais frequentemente encontrada em parede abdominal, períneo e extremidades. Raros casos foram descritos na mama e a literatura aponta a amamentação e procedimentos mamários prévios como fatores de riscos para essa condição. Apresentamos uma paciente no puerpério, de 27 anos, que apresentou uma fissura no mamilo direito associada à amamentação e que evoluiu com infecção local agressiva, com necrose extensa de fáscias e parênquima mamário caracterizada como fasciíte necrotizante. O trabalho visa apresentar a importância do diagnóstico precoce, principalmente com diferenciação para as mastites puerperais que possuem fisiopatologia e tratamento distintos, assim como a necessidade do tratamento adequado com desbridamento cirúrgico e antibioticoterapia de amplo espectro para evitar maiores complicações e o óbito

Oncological safety of autologous fat grafting after breast conservative treatment: a prospective evaluation.

Autologous fat graft to the breast is a useful tool to correct defects after breast conservative treatment (BCT). Although this procedure gains popularity, little is known about the interaction between the fat graft and the prior oncological environment. Evidences of safety of this procedure in healthy breast and after post-mastectomy reconstruction exist. However, there is paucity of data among patients who underwent BCT which are hypothetically under a higher risk of local recurrence (LR). Fifty-nine patients, with prior BCT, underwent 75 autologous fat graft procedures using the Coleman's technique, between October 2005 and July 2008. Follow-up was made by clinical and radiologic examination at least once, after 6 months of the procedure. Mean age was 50 ± 8.5 years, and mean follow-up was 34.4 ± 15.3 months. Mean time from oncological surgery to the first fat grafting procedure was 76.6 ± 30.9 months. Most of patients were at initial stage 0 (11.8%), I (33.8%), or IIA (23.7%). Immediate complication was observed in three cases (4%). Only three cases of true LR (4%) associated with the procedure were observed during the follow-up. Abnormal breast images were present in 20% of the postoperative mammograms, and in 8% of the cases, biopsy was warranted. Autologous fat graft is a safe procedure to correct breast defects after BCT, with low postoperative complications. Although it was not associated with increased risk of LR in the group of patients studied, prospective trials are needed to certify that it does not interfere in patient's oncological prognosis.

Sarcoid-like reaction in breast cancer: a long-term follow-up series of eight patients.

PURPOSE: Finding an intrathoracic or axillary mass in a breast cancer patient should raise suspicion of a pulmonary or mediastinal nodal metastasis or axillary recurrence. Surprisingly, noncaseating epithelioid cell granuloma can be found in this type of lesion, as in sarcoidosis or a sarcoid-like reaction. METHODS: This series included eight breast cancer patients in whom a late sarcoid-like reaction developed: as an intrathoracic lesion in six, and as an ipsilateral axillary lesion in two. The latency period from oncological surgery to the diagnosis of sarcoidosis was 40 months and the average follow-up after the diagnosis of sarcoidosis was 63.38 months. RESULTS: None of the patients suffered relapse or oncological events during the period of this study. CONCLUSION: To avoid misdiagnosis and overtreatment, pathological examination should always be carried out. We do not recommend any specific treatment for sarcoidosis in a breast cancer patient, but routine oncological follow-up is appropriate. A larger series with statistical analysis is necessary to evaluate the prognosis.