Genomic characterisation of breast fibroepithelial lesions in an international cohort.

Fibroepithelial lesions (FELs) are a heterogeneous group of tumours comprising fibroadenomas (FAs) and phyllodes tumours (PTs). Here we used a 16-gene panel that was previously discovered to be implicated in pathogenesis and progression, to characterise a large international cohort of FELs via targeted sequencing. The study comprised 303 (38%) FAs and 493 (62%) PTs which were contributed by the International Fibroepithelial Consortium. There were 659 (83%) Asian and 109 (14%) non-Asian FELs, while the ethnicity of the rest was unknown. Genetic aberrations were significantly associated with increasing grade of PTs, and were detected more in PTs than FAs for MED12, TERT promoter, RARA, FLNA, SETD2, TP53, RB1, EGFR, and IGF1R. Most borderline and malignant PTs possessed ≥ 2 mutations, while there were more cases of FAs with ≤ 1 mutation compared to PTs. FELs with MED12 mutations had significantly higher rates of TERT promoter, RARA, SETD2, EGFR, ERBB4, MAP3K1, and IGF1R aberrations. However, FELs with wild-type MED12 were more likely to express TP53 and PIK3CA mutations. There were no significant differences observed between the mutational profiles of recurrent FAs, FAs with a history of subsequent ipsilateral recurrence or contralateral occurrence, and FAs without a history of subsequent events. We identified recurrent mutations which were more frequent in PTs than FAs, with borderline and malignant PTs harbouring cancer driver gene and multiple mutations. This study affirms the role of a set of genes in FELs, including its potential utility in classification based on mutational profiles. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Fibroadenoma: Accuracy of clinical diagnosis in females aged 25 years or less.

BACKGROUND: Accurate clinical diagnosis of fibroadenoma in young females is desirable because of the possibility of nonoperative treatment for those desiring it. OBJECTIVES: To determine the accuracy of the clinical diagnosis of fibroadenoma in patients aged ≤ 25 years. PATIENTS AND METHODS: A prospective study of all patients with breast disease presenting to the breast clinic was conducted from January 2004 to December 2008. RESULTS: During the study period, 145 patients aged ≤25 years presented with breast lumps. In this group, a clinical diagnosis of fibroadenoma was made in 100 (69.0%), fibrocystic disease in 32 (22.1%), breast cancer in 4 (0.03%) patients, the remaining were benign lesions. Excision biopsy was done for 81 (55.9%) patients. Of these 81 patients, only 62 (76.5%) returned with histology report. The histological diagnosis was fibroadenoma in 45 (72.5%) patients with a mean age of 21.4 years. Their ages range from 18 to 25 years. The histological diagnosis was fibrocystic disease in 9 (14.5%) and malignant phyllodes in 1 (1.6%) patient. The remaining 7 (11.3%) patients had other types of benign lesions. For fibroadenoma, true positive cases were 42, false positive 7 and false negative 3, and true negative 10. Therefore, the sensitivity of clinical diagnosis of fibroadenoma was 93.3%, while specificity was 58.8%. CONCLUSION: The sensitivity of clinical diagnosis of fibroadenoma in patients aged ≤25 years was good, though specificity is low.

Biomarkers of dietary exposure are associated with lower risk of breast fibroadenomas in Chinese women.

Fibroadenomas are the most common benign breast condition among women and account for up to 50% of all breast biopsies being performed. Although considered a benign condition, fibroadenomas utilize substantial resources for management and treatment to rule out potential malignancies. Dietary factors may influence benign fibrocystic breast conditions, but little is known of their association with fibroadenomas. We examined possible associations between a broad spectrum of circulating biomarkers of dietary intake and risk of fibroadenomas. Participants were women in a breast self-examination trial in Shanghai, China who were diagnosed with fibroadenomas (n = 258) and 1035 controls. Conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% CI. Isoflavone concentrations were inversely associated with risk of fibroadenomas. Adjusted OR (95% CI) for the highest versus the lowest quartile of plasma concentration were 0.36 (0.16-0.79; P-trend < 0.001) for daidzein and 0.39 (0.19-0.84; P-trend = 0.010) for genistein. We also observed inverse associations between higher percentages of the RBC (n-3) fatty acids, eicosapentaenoic acid (EPA) ([0.38 (0.19-0.77); P-trend = 0.007] and docosapentaenoic acid (DPA) [0.32 (0.15-0.70); P-trend = 0.024], and fibroadenoma risk. Circulating concentrations of carotenoids, vitamin C, retinol, and ferritin were not associated with fibroadenoma risk. The inverse associations between plasma isoflavone concentrations and RBC EPA and DPA and fibroadenoma risk suggest that higher intakes of soy foods and fatty fish may lower the risk of fibroadenomas.

Fruit and vegetable intakes are associated with lower risk of breast fibroadenomas in Chinese women.

Fibroadenomas are common benign breast conditions among women and account for approximately 50% of breast biopsies performed. Dietary factors are known to influence benign breast conditions in the aggregate, but little is known of their association specifically with fibroadenoma. Our objective in this study was to evaluate the association between dietary and other factors and fibroadenoma risk. A case-control study, nested in a randomized trial of breast self-examination (BSE) in Chinese textile workers in Shanghai, China, was conducted between 1989 and 2000. The study sample included 327 affected women and 1070 controls. Women were administered a FFQ and a questionnaire that elicited reproductive and gynecological history and other information. Odds ratios, as estimates of relative risks, were calculated using multivariate conditional logistic regression. Significant decreasing trends in risk of fibroadenoma were observed with intake of fruits and vegetables and with number of live births, and a reduced risk was also associated with natural menopause, oral contraceptive use, and moderate exercise (walking and gardening). Increased risk of fibroadenoma was associated with heavy physical activity in one's 20s, breast cancer in a first-degree relative, and a history of prior benign breast lumps; and significant increasing trends in risk were observed with numbers of BSE per year and years of education. In conclusion, a diet rich in fruits and vegetables and the use of oral contraceptives may reduce risk of fibroadenoma.

Fibroadenomas in adolescence.

PURPOSE OF REVIEW: Fibroadenomas are the most common breast masses in adolescent women, therefore it is important that health providers understand their assessment and management. This review discusses an approach to investigation and management of fibroadenomas in adolescents. RECENT FINDINGS: Fibroadenomas are benign tumors which commonly present in late adolescence. They are classified according to their histology and size. Simple fibroadenomas are the most common type and usually present as smooth mobile masses up to 3 cm in diameter. Giant fibroadenomas are more uncommon but typically present in adolescence. Fibroadenomas associated with other soft-tissue masses should raise the possibility of an inherited syndrome. Assessment of breast masses in this age group generally involves clinical assessment through history and physical examination and, when imaging is needed, ultrasonography. As the incidence of primary breast malignancy is very low in this age group, core biopsy is not routinely recommended. Large or rapidly growing tumors, or those associated with suspicious features, warrant surgical excision. New minimally invasive excision techniques are being introduced which are associated with high initial success rates. SUMMARY: Whereas the vast majority of fibroadenomas in teenagers may be monitored with surveillance alone, new minimally invasive techniques may play an important role in the management of selected patients.

Risk factors for breast cancer from benign breast disease in a diverse population.

BACKGROUND: The majority of studies have reported risks of breast cancer (BC) from benign breast disease (BBD) in essentially homogenous Caucasian populations. Information on breast cancer risk factors in larger, multi-ethnic populations should facilitate the development of appropriate and targeted risk reduction strategies. DESIGN: Cases and controls were drawn from a parent BBD cohort of 4,970 women, 1,341 African-Americans (AA) and 3,629 non-AA who were diagnosed with BBD after examination of an excisional breast biopsy. Risk factors (34 variables) included demographics, lesion types, and epidemiological variables. RESULTS: The final multivariable model retained significance (P < 0.05) for lesion risk-level, fibroadenoma, and the interaction of age-by-race. Women with proliferative lesions (no atypia, risk level 2) were 1.7 times more likely to develop BC when compared with women with non-proliferative lesions (OR = 1.7, 95% CI 1.13, 2.42, P = 0.009). Women with atypia (risk level 3) were 3.75 times more likely to develop BC compared to women with non-proliferative lesions (OR = 3.75, 95% CI 1.99, 7.06, P < 0.001). The odds of breast cancer was approximately 35% lower among women with fibroadenoma as compared to women without fibroadenoma (OR = 0.65, 95% CI 0.46, 0.94, P = 0.020). AA women with BBD who were 50 years or older were 2.28 times more likely to develop breast cancer as compared to non-AA women who were less than 50 years old (OR = 2.28, 95% CI 1.34, 3.88, P = 0.002). CONCLUSION: Women with fibroadenoma (nonproliferative or proliferative) were less likely to progress to BC. Older AA women are at greater risk for progression to breast cancer from BBD.

Expression of the serine protease, matriptase, in breast ductal carcinoma of Chinese women: correlation with clinicopathological parameters.

Matriptase is a serine protease expressed by cells of surface epithelial origin, including epithelial breast tumor cells. Matriptase cleaves and activates proteins implicated in the progression of cancer and represents a potential prognostic and therapeutic target. The aim of this study was to examine matriptase expression in breast tumors of Chinese women and to identify its clinicopathological correlations. Immunohistochemical analysis of matriptase was performed in tissue microarrays of 251 breast tumors including 30 fibroadenomas, 59 ductal carcinomas in situ (DCIS), 38 grade I invasive ductal carcinomas (IDC), 79 grade II IDC, and 45 grade III IDC. The matriptase scores were significantly higher in the tumors than their non-tumor counterparts (178+/-12 for fibroadenoma; 275+/-11 for DCIS; 299+/-10 for grade I IDC; 251+/-10 for grade II IDC; and 314+/-11 for grade III IDC). In cases of IDC, matriptase scores were significantly correlated with tumor staging and nodal staging. Our findings demonstrate that matriptase is over-expressed in breast ductal carcinoma of Chinese women. It therefore may be a good biomarker for diagnosis and treatment of malignant breast tumors.

Fibro-adenoma of the breast in Nigerian Igbos.

BACKGROUND: There has been a recent increase in interest in conservative treatment of benign disease. OBJECTIVE: To study the epidemiology, clinical features and management of fibro-adenoma of the breast in Nigerian Igbos. PATIENTS AND METHODS: Patients with breast disease presenting to the author at four Nigerian hospitals between 1986 and 1997 were enrolled in a prospective study. RESULTS: Patients with breast disease constituted a significant burden in general surgical practices, with fibro-adenoma present in 94 out of 284 patients with benign disease (33%) and 410 patients with breast disease (23%). The accuracy of clinical pre-operative diagnosis is excellent, especially in those aged under 25 years. Conservative treatment may be advisable for these patients if they can be kept under observation. Other worrisome discoveries include a high rate of teenage abortion and a significant delay in seeking medical help that has not reduced when compared with a previous study undertaken 30 years ago.

A new BRCA1 mutation in a Filipino woman with a family history of breast and ovarian cancer.

Mutation of the BRCA1 gene in well-defined breast cancer families has been associated with an 87% lifetime risk for breast cancer and a 44% risk for ovarian cancer. Recent data indicate that the risk associated with these mutations is considerably lower, although still far greater than the risk for disease in the rest of the population. Approximately 81% of the mutations that have been identified have been frameshift (71%) or nonsense (10%) mutations, and either may result in a truncated protein. The protein truncation test (PTT) is often used to screen patients at high risk, because sequencing of this large (100 kb) gene with its 22 coding exons is an arduous task. The PTT was used to analyze genomic DNA and RNA from the peripheral blood of a 31-year-old Filipino woman with a poorly differentiated, stage 2A breast carcinoma and a family history of breast-ovarian cancer. PTT identified the wild-type protein fragment and an additional truncated protein fragment in the patient's sample. Subsequent direct sequencing of the appropriate coding region revealed a point mutation in exon 11 at nucleotide 2178, resulting in a C > T transition that caused a termination (stop codon) in amino acid 687. To our knowledge, this is the first report of mutation of the BRCA1 gene in a Filipino family, and this in-frame stop-codon mutation has not been reported previously.