scholarly journals Molecular features of premenopausal breast cancers in Latin American women: pilot results from the PRECAMA study

2018 ◽  
Author(s):  
Magali Olivier ◽  
Liacine Bouaoun ◽  
Stephanie Villar ◽  
Alexis Robitaille ◽  
Vincent Cahais ◽  
...  

AbstractBackgroundIn Latin America (LA), there is a high incidence rate of breast cancer (BC) in premenopausal women, and the genomic features of these BC remain unknown. Here, we aim to characterize the molecular features of BC in young LA women within the framework of the PRECAMA study, a multicenter population-based case-control study on breast cancer in premenopausal women.MethodsPathological tumor tissues were collected from incident cases from four LA countries. Immunohistochemistry (IHC) was performed centrally for ER, PR, HER2, Ki67, EGFR, CK5/6 and p53 protein markers. Targeted deep sequencing was done on genomic DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour tissues and their paired blood samples to screen for somatic mutations in eight genes frequently mutated in BC. A subset of samples was analyzed by exome sequencing to identify somatic mutational signatures.ResultsThe majority of cases were positive for ER or PR (168/233; 72%) and there were 21% triple negative (TN) cases, mainly of basal type. Most tumors were positive for Ki67 (189/233; 81%). In 126 sequenced cases,TP53andPIK3CAwere the most frequently mutated genes (32.5% and 21.4%, respectively), followed byAKT1(9.5%).TP53mutations were more frequent in HER2-enriched and TN IHC subtypes, whilePIK3CA/AKT1mutations were more frequent in ER positive tumors, as expected. Interestingly, a higher proportion of G:C>T:A mutations was observed inTP53gene in PRECAMA cases compared to TCGA and METABRIC breast cancer series (27% vs 14%). Exome-wide mutational patterns in 10 TN cases revealed alterations in signaling transduction pathways and major contributions of mutational signatures caused by altered DNA repair pathways.ConclusionsThis pilot results on PRECAMA tumors gives a preview of the molecular features of premenopausal BC in LA. Although, the overall mutation burden was as expected from data in other populations, mutational patterns observed inTP53and exome-wide suggested possible differences in mutagenic processes giving rise to these tumors compared to other populations. Further omics analyses of a larger number of cases in the near future will allow investigating relationships between these molecular features and risk factors.

2005 ◽  
Vol 91 (6) ◽  
pp. 505-512 ◽  
Author(s):  
Antonino Musolino ◽  
Maria Michiara ◽  
Maria A. Bella ◽  
Nadia Naldi ◽  
Paola Zanelli ◽  
...  

Purpose To evaluate the clinical features of breast cancer patients with genetic susceptibility to this disease and to investigate the contribution of BRCA1 germline mutations to the phenotype of these tumors. Patients and Methods We reviewed the clinical and pathological records of 102 women with suspected inherited susceptibility to breast cancer consecutively seen at the Genetic Oncology Service of Parma, Italy. Sixty-two patients with a high probability of harboring a germline, cancer-predisposing mutation were tested for BRCA1 mutations. Exon 11 was screened using the protein truncation test and detected mutations were confirmed by direct sequencing (DS). All other exons were analyzed by DS. Results Among the 62 patients with a completed mutation analysis, 48 (77.4%) had wild-type BRCA1, six (9.6%) had variants of unclear significance, eight (13%) had deleterious mutations. BRCA1-associated breast cancers (BABC) were significantly less likely to be diagnosed at stage I than breast cancers in women without mutations (12.5% vs 51%; P = 0.045), more likely to have a high proliferation rate (100% vs 24%, P<0.001), and more likely to be histological grade 3 (100% vs 14%, P<0.001), estrogen and progesterone receptor negative (87.5% vs 13%, P<0.001; 75% vs 23%, P = 0.004), and p53 positive (87.5% vs 30%, P = 0.023). All tumors with BRCA1 mutations were HER-2/neu negative compared with 57% of the non-BRCA1 tumors ( P = 0.04). There were no significant differences between BABC and non-BABC in 20-year relapse-free survival, 20-year event-free survival, and 20-year overall survival. Conclusion In this population-based study, BABC seems to present with adverse molecular features when compared with non-BABC, although the prognosis appears to be similar.


1987 ◽  
Vol 73 (3) ◽  
pp. 219-227 ◽  
Author(s):  
Alberto Pier Mario Cappa ◽  
Giancarlo Bertiond ◽  
Alessandro Colombo ◽  
Fabrizio Faggiano ◽  
Margherita Gussio ◽  
...  

A population-based survey of histologically diagnosed breast cancer was carried out among residents in Piedmont. A total of 5267 incident cases occurring in 1979–1981 was collected, corresponding to an age-standardized (on the world population) incidence rate of 49.5/100,000 per year. Rates (standardized on the population of Piedmont in 1981) were highest in the city of Torino (112.4/100,000 per year) and lowest in the province of Cuneo (67.5), whereas in the other provinces they ranged between 85.3 and 90.0. Estimation of rates in the 54 Local Health Authorities of Piedmont detected up to 2-fold differences between adjacent areas. A correlation was found between rates and size of the population of town of residence. Comparison with age-specific incidence rates from the Cancer Registry of the nearby province of Varese suggested a loss of nonhistologically confirmed cases selectively in older age groups. The distribution of cases diagnosed in 1979 by histologic type is presented. The proportion of diagnoses reported in terms which were consistent with the 1978 WHO Histological Typing of Breast Tumours was 61.3%. It was highest among cases identified in Pathology Services located in University Hospitals and/or diagnosing more than 50 breast cancers per year.


Author(s):  
Hsing-Chi Hsu ◽  
Kai-Yu Tseng ◽  
Hsiang-Chi Wang ◽  
Fung-Chan Sung ◽  
Wei-Fen Ma

Background: Endometriosis has been associated with the subsequent development of ovarian and breast cancers. This study evaluated whether nurses were at increased risks of developing endometriosis and subsequent ovarian and breast cancers. Methods: From Taiwan National Health Insurance Research Database during 2000 to 2011, we established 3 study cohorts, consisting of 23,801 nurses, 11,973 other hospital employees, and 143,096 general women free of endometriosis and cancer. Women in all cohorts were followed to the end of 2011 to measure the occurrences of endometriosis and subsequent ovarian and breast cancers. The incident endometriosis cases and related hazard ratio (HR) and 95% confidence interval (CI) were calculated. The incident cases of ovarian cancer and breast cancer and related odds ratio were calculated. Results: The incidence of endometriosis was the highest in the nurse cohort (4.23 per 100, n = 966) followed by other health professionals (3.74 per 100, n = 427) and control cohort (3.06 per 100, n = 4193), with adjusted hazard ratios of 1.28 (95% CI = 1.20–1.38) and 1.13 (95% CI = 1.02–1.25), respectively, comparing to controls. Among those who developed endometriosis, nurses had higher subsequent ovarian cancer and lower breast cancer, but not significant. Conclusions: Nurses are at a higher risk of developing endometriosis. However, the link between endometriosis and subsequent cancers is weak.


1994 ◽  
Vol 80 (4) ◽  
pp. 263-268
Author(s):  
Stefania Rodella ◽  
Monica Turazza ◽  
Cosimo Picoco ◽  
Franco Stanziai ◽  
Franco Bonetti ◽  
...  

Aims and background The role of distribution by stage at diagnosis in breast cancer has been considered in many studies, with particular regard to evaluation of prognosis, impact of screening programs and quality of care. Nevertheless, international comparisons of descriptive data can be hampered by lack of homogeneity in staging methods. The TNM is presently the most common staging system used all over the world, although some criticism have been raised recently against its pragmatic value. The present study reports a population-based survey of pathologic TNM distribution in incident cases of female breast cancer in the Verona province, a geographical area of northern Italy covered by cancer registration. Methods All histologically proven incident cases of breast cancer were identified in the study period 1988-1990 and classified as for tumor size and nodal involvement according to the pathological TNM criteria. The type of surgical treatment was also registered for all cases diagnosed in 1990. Results one thousand two hundreds and fifty-four invasive and in situ breast cancers were observed and pT1 cases accounted for 44.4%. Nodal involvement was present in 41.5% of invasive cancers. A surgical treatment was performed in 1213 patients (96.7%). Axillary dissection was reported in 1080 cases, 820 of them (76.6%) having 10 or more lymph nodes examined. Radical mastectomy accounted for 74% of the 458 breast cancers diagnosed in 1990 and 31.6% of the eligible cases were conservatively treated. Conclusions Cancer registries should be encouraged to report data on stage distribution in breast cancer (and in other malignancies). This practice could improve international comparisons and give an essential contribution to studies on survival, screening programs and quality of care.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 519-519 ◽  
Author(s):  
M. Cheang ◽  
S. K. Chia ◽  
D. Tu ◽  
S. Jiang ◽  
L. E. Shepherd ◽  
...  

519 Background: MA5 randomized premenopausal women with node-positive early breast cancers to cyclophosphamide- methotrexate-fluorouracil (CMF) or cyclophosphamide-epirubicin-fluorouracil (CEF) adjuvant chemotherapy. This and other trials have shown that adjuvant regimens containing anthracyclines confer significant survival benefit to breast cancer patients. Meta-analyses have revealed most benefit in women with HER2(+) or TOPO2 (+) tumors. Population-based data suggest that patients with a core basal phenotype (negative for hormone receptors and HER2, positive for CK5/6 or EGFR) conversely have worse survival on anthracycline containing vs. CMF regimens. Here we test the hypothesis specified a priori that for basal breast cancers anthracyclines may be inferior, using data from MA5. Methods: From 710 patients in MA5, blocks suitable for tissue microarray construction were recovered for 549. Immunohistochemistry for ER, PR, HER2, Ki67, CK5/6 and EGFR was obtained, allowing stratification of 511 cases into intrinsic biological subtypes by published methods (Cheang MC et al. Clin Cancer Res 2008;14:1368–76). Prespecified analyses were conducted independently by the NCIC- CTG statistical centre. Results: In the CEF arm, patients with core basal tumors had a hazard ratio of 1.8 (log rank p=0.02) for overall survival (OS) relative to the other biological subtypes. In the CMF arm, there was no significant difference (HR 0.9, p = 0.7). The interaction between core basal status and treatment was borderline significant (p=0.06). Relapse free survival differences did not reach significance. Conclusions: Data from this randomized trial supports the hypothesis that anthracycline containing adjuvant chemotherapy regimens are inferior to adjuvant CMF in women with basal breast cancer. [Table: see text] No significant financial relationships to disclose.


Author(s):  
Stephanie C Melkonian ◽  
Hannah K Weir ◽  
Melissa A Jim ◽  
Bailey Preikschat ◽  
Donald Haverkamp ◽  
...  

Abstract Cancer incidence varies among American Indian and Alaska Native (AI/AN) populations, as well as between AI/AN and White populations. This study examined trends for cancers with elevated incidence among AI/AN compared with non-Hispanic White populations and estimated potentially avoidable incident cases among AI/AN populations. Incident cases diagnosed during 2012–2016 were identified from population-based cancer registries and linked with the Indian Health Service patient registration databases to improve racial classification of AI/AN populations. Age-adjusted rates (per 100,000) and trends were calculated for cancers with elevated incidence among AI/AN compared with non-Hispanic White populations (rate ratio &gt;1.0), by region. Trends were estimated using joinpoint regression analyses. Expected cancers were estimated by applying age-specific cancer incidence rates among non-Hispanic White populations to population estimates for AI/AN populations. Excess cancer cases among AI/AN populations were defined as observed minus expected cases. Liver, stomach, kidney, lung, colorectal and female breast cancers had higher incidence rate among AI/AN populations across most regions. Between 2012 and 2016, nearly 5,200 excess cancers were diagnosed among AI/AN populations, with the largest number of excess cancers (1,925) occurring in the Southern Plains region. Culturally informed efforts may reduce cancer disparities associated with these and other cancers among AI/AN populations.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dechuang Jiao ◽  
Jingyang Zhang ◽  
Jiujun Zhu ◽  
Xuhui Guo ◽  
Yue Yang ◽  
...  

Abstract Background Previous studies have reported poor survival rates in inflammatory breast cancer (IBC) patients than non-inflammatory local advanced breast cancer (non-IBC) patients. However, until now, the survival rate of IBC and other T4 non-IBC (T4-non-IBC) patients remains unexplored. Methods Surveillance, Epidemiology, and End Results (SEER) database was searched to identify cases with confirmed non-metastatic IBC and T4-non-IBC who had received surgery, chemotherapy, and radiotherapy between 2010 and 2015. IBC was defined as per the American Joint Committee on Cancer (AJCC) 7th edition. Breast Cancer-Specific Survival (BCSS) was estimated by plotting the Kaplan-Meier curve and compared across groups by using the log-rank test. Cox model was constructed to determine the association between IBC and BCSS after adjusting for age, race, stage of disease, tumor grade and surgery type. Results Out of a total of 1986 patients, 37.1% had IBC and mean age was 56.6 ± 12.4. After a median follow-up time of 28 months, 3-year BCSS rate for IBC and T4-non-IBC patients was 81.4 and 81.9%, respectively (log-rank p = 0.398). The 3-year BCSS rate in HR−/HER2+ cohort was higher for IBC patients than T4-non-IBC patients (89.5% vs. 80.8%; log-rank p = 0.028), and in HR−/HER2- cohort it was significantly lower for IBC patients than T4-non-IBC patients (57.4% vs. 67.5%; log-rank p = 0.010). However, it was identical between IBC and T4-non-IBC patients in both HR+/HER2- (85.0% vs. 85.3%; log-rank p = 0.567) and HR+/HER2+ (93.6% vs. 91.0%, log-rank p = 0.510) cohorts. After adjusting for potential confounding variables, we observed that IBC is a significant independent predictor for survival of HR−/HER2+ cohort (hazards ratio [HR] = 0.442; 95% CI: 0.216–0.902; P = 0.025) and HR−/HER2- cohort (HR = 1.738; 95% CI: 1.192–2.534; P = 0.004). Conclusions Patients with IBC and T4-non-IBC had a similar BCSS in the era of modern systemic treatment. In IBC patients, the HR−/HER2+ subtype is associated with a better outcome, and HR−/HER2- subtype is associated with poorer outcomes as compared to the T4-non-IBC patients.


2001 ◽  
Vol 119 (2) ◽  
pp. 62-66 ◽  
Author(s):  
Anelise Bezerra de Vasconcelos ◽  
Gulnar Azevedo e Silva Mendonça ◽  
Rosely Sichieri

CONTEXT: The relationship between body size and breast cancer still remains controversial in considering menopausal status. OBJECTIVE: To evaluate the association of height, weight and weight changes with breast cancer in the city of Rio de Janeiro, Brazil. DESIGN: Case-control study. SETTING: National Cancer Institute (INCA), Rio de Janeiro, Brazil, and State University of Rio de Janeiro (UERJ). SAMPLE: 177 incident cases of invasive breast cancer admitted to the main hospital of INCA between May 1995 and February 1996, and 377 controls recruited from among female visitors to the same hospital. MAIN MEASUREMENTS: Height and weight were measured and information on maximum weight, weight at ages 18 and 30 years, and potential risk factors were ascertained by interview at the hospital. RESULTS: Height was not related to risk of breast cancer among both pre and postmenopausal women. Nevertheless, women in this study were shorter than in studies that have found a positive association. Premenopausal women in the upper quartile of recent body mass index (BMI) and maximum BMI showed a reduced risk of breast cancer (P for trend <= 0.03). Weight loss between ages 18 and 30 years and from 18 years to present was also associated with breast cancer among premenopausal women. CONCLUSIONS: These findings may merely indicate the known association between leanness and breast cancer. Further studies should explore the role of weight loss on breast cancer risk.


2021 ◽  
Author(s):  
Juliana Fernandes ◽  
Beatriz Machado ◽  
Cassio Cardoso-Filho ◽  
Juliana Nativio ◽  
Cesar Cabello ◽  
...  

Abstract Background This study aims to assess breast cancer survival rates after one decade of mammography in a large urban area of Brazil. Methods It is a population-based retrospective cohort of women with breast cancer in Campinas, São Paulo, from 2010 to 2014. Age, vital status and stage were accessed through the cancer and mortality registry, and patients records. Statistics used Kaplan-Meier, log-rank and Cox's regression. Results Out of the 2,715 cases, 665 deaths (24.5%) were confirmed until early 2020. The mean age at diagnosis was 58.6 years. Women 50-69 years were 48.0%, and stage I the most frequent (25.0%). The overall mean survival was 8.4 years (8.2-8.5). The 5-year survival (5yOS) for overall, 40-49, 50-59, 60-69, 70-79 years was respectively 80.5%, 87.7%, 83.7%, 83.8% and 75.5%. The 5yOS for stages 0, I, II, III and IV was 95.2%, 92.6%, 89.4%, 71.1% and 47.1%. There was no significant difference in survival in stage I or II (p=0.058). Compared to women 50-59 years, death's risk was 2.3 times higher for women 70-79 years and 26% lower for women 40-49 years. Concerning stage I, the risk of death was 1.5, 4.1 and 8.6 times higher, and 34% lower, respectively, for stage II, III, IV and 0. Conclusions In Brazil, breast cancers are currently diagnosed in the early stages, although advanced cases persist. Survival rates may reflect improvements in screening, early detection and treatment. The results can reflect the current status of other regions or countries with similar health care conditions.


2016 ◽  
Vol 12 (11) ◽  
pp. 1148-1156 ◽  
Author(s):  
Amye J. Tevaarwerk ◽  
Kari B. Wisinski ◽  
Ruth M. O’Regan

Systemic therapy for premenopausal women with hormone receptor–positive breast cancer has evolved in the last 5 years, but critical questions remain. Recent randomized trials have demonstrated a benefit for the addition of ovarian suppression to endocrine therapy in patients with breast cancers considered to be at high risk for recurrence, whereas those with lower-risk cancers seem to have a favorable outcome with tamoxifen alone. Two large randomized trials have demonstrated a benefit for extending adjuvant tamoxifen beyond 5 years. Currently the choice of systemic therapy is selected empirically but molecular profiling may, in the near future, provide a more conclusive means of selecting an endocrine therapeutic approach for premenopausal patients. Given that a significant subset of hormone receptor–positive cancers are intrinsically resistant to endocrine agents, as well as the finding that inhibiting cyclin-dependent kinases 4 and 6 and mammalian target of rapamycin appears to potentially reverse this resistance in patients with metastatic disease, evaluation of these agents in the early-stage setting is ongoing.


Sign in / Sign up

Export Citation Format

Share Document