Breast cancer prognosis in BRCA1/2  mutation carriers: A case control study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1554-1554
Author(s):  
Grazia Arpino ◽  
Matilde Pensabene ◽  
Valeria Forestieri ◽  
Caterina Condello ◽  
Maria Anna Sarno ◽  
...  

1554 Background: We evaluated the clinical impact of germ-line BRCA1/2 mutations and variants of unknown clinical significance (VUS) for BRCA1/2 in patients (pts) with early breast cancer (BC). Methods: Twenty-eight BRCA-positive (BRCA+) BC pts with germ-line BRCA1 /2 mutations and 16 VUS BC pts were selected from our database and matched (1:3) with 154 nonhereditary BC controls (sporadic controls, SC, defined by no associated personal history of breast cancer and no family history of breast and ovarian cancer or an uninformative BRCA mutation test) for stage, histologic subtype, age, and year of diagnosis. Clinical characteristics, recurrence (rec) pattern, disease free survival (DFS) and overall survival (OS) were analyzed. Results: Compared with VUS and SC, BRCA+ pts were less likely to express estrogen receptor (64% vs. 89% vs. 54% respectively p<.005) and progesterone receptor (64% vs. 86% vs. 59% respectively p<.005) but more likely to be triple negative (0 vs. 3.4% vs 47.4% respectively p<.005). Compared with VUS and SC, BRCA+ pts were more likely treated by radical mastectomy (37.5% vs. 26.4% vs. 59.3% % respectively p<.005). Pattern of rec was also different. Compared with VUS and SC, BRAC+ pts developed more second tumors (11% vs. 6.3% vs. 1.9% respectively p<.0001) but less local or distant rec (31% vs. 2.6 vs. 0% for local rec and 12% vs. 16% vs. 11% for distant rec respectively p<.0001). Controlateral BC was more frequent in VUS compared to the BRAC+ and SC pts (12% vs. 7% vs. 1% respectively, p<.0001). At a median follow up of 88 months, at univariate analysis, BRAC+ but not VUS pts had worse OS compared to SC (p=.006). No difference in DFS was observed for VUS or BRAC+ when compared to SC pts. After adjustment for age, stage, grade, nodal status, hormone receptors, adjuvant therapy and year of diagnosis, BRCA+ pts continued to have and increased risk of death compared to SC (HR 5.9, 95% CI 1.9-18.1, p<.002). Most of the deaths observed in BRAC+ pts were not cancer related. Conclusions: Despite decrease incidence of local or distant recs, BRAC+ pts seems to be more likely to die compared to SC. Development of second cancers and unknown effects of BRCA1/2 mutations on nonneoplastic diseases that cause death may account for this findings.

2017 ◽  
Vol 83 (8) ◽  
pp. 887-894 ◽  
Author(s):  
Ameliay Merrill ◽  
Doris R. Brown ◽  
Heidi D. Klepin ◽  
Edward A. Levine ◽  
Marissa Howard-Mcnatt

Prospective studies have shown equal outcomes after mastectomy or breast conservation in patients with invasive breast cancer; however, many of these studies excluded elderly patients. We identified patients in their eighties and nineties with clinical stage 0 to II breast cancer undergoing mastectomy or lumpectomy with or without radiation from the prospective sentinel lymph node database at Wake Forest Baptist Health and analyzed their treatment and survival. Of 92 patients, 24 (26.1%) underwent mastectomy, 22 (23.9%) lumpectomy with radiation, and 46 (50.0%) lumpectomy alone. Significant differences were noted in tumor size (P = 0.018), nodal status (P = 0.013), and stage (P = 0.011) between the groups. Only 7.6 per cent of patients had chemotherapy, whereas 51.1 per cent took antiestrogen therapy. Recurrence occurred in 11 patients. In univariate analysis, overall survival did not differ by surgery. Age was the only factor that increased risk of death (HR = 1.19, P = 0.028). In this age group, neither tumor factors nor the type of local treatment significantly influenced overall survival. Octogenarians and nonagenarians with early-stage breast cancer undergoing breast-conserving surgery with or without radiation have equivalent survival to patients having a mastectomy.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 355-355 ◽  
Author(s):  
Christopher Michael Tully ◽  
Bernard H. Bochner ◽  
Guido Dalbagni ◽  
Emily C. Zabor ◽  
Harry W. Herr ◽  
...  

355 Background: NAC and RC-PLND improves survival in MIBC and GC is a standard NAC option. However, little is known about GC efficacy endpoints and the individual contribution of NAC and surgery. Methods: Pts with clinical T2-T4aN0M0 MIBC treated from 1/2000 to 10/2012 with a planned 4 cycles of GC plus RC-PLND within 90 days (D) of NAC were evaluated retrospectively for the number (#) of cycles, dose delivered, D from end of NAC to RC-PLND, margin status, LN status and # of LN identified. Post-NAC pathologic endpoints included complete response (pT0), residual Non-MIBC disease (pTa/Tis/T1;N0) and ≥MIBC disease (≥pT2N0). Associations with overall survival (OS) and disease-free survival were analyzed using Cox regression; non-linear associations with # of resected LN used linear and quadratic terms. Results: 154 pts met inclusion criteria. 5-year (yr) OS was 61% (95% CI 53-71%). Post-NAC pT0 was achieved in 21% (32/154) and Non-MIBC in 25% (39/154 - pTa (2), pTis (25), pT1 (12)). Post-NAC pT0 and Non-MIBC had similar 5-yr OS (85% and 89%, respectively) and combined (<pT2) pts differed significantly from pts with ≥pT2, (87% (95% CI 78, 98%) and 38% (95% CI 27, 53%), respectively; p<0.001). Median D from NAC to RC-PLND was 34 and median # of resected LN was 19. On univariate analysis, # of cycles (4 vs <4), GC dose intensity and total dose, clinical stage (cT2 vs cT3/cT4), # of resected LN, positive (+) LN and + margins were significant for OS. In multivariate analysis, post-NAC pathology ≥pT2 (HR 6.7; 95% CI 2.6-17.4; p<0.001), + LN (HR 3.21; 95% CI 1.6-6.4; p=0.001) and + margins (HR 3.2; 95% CI 1.4-7.5; p=0.007) were significant for increased risk of death. Using a model with these 3 predictors to estimate the benefit of PLND, the hazard ratio decreased with each LN resected until 25 and then plateaued beyond 25 (p=0.016). Conclusions: NAC with GC has excellent drug delivery, permits rapid RC-PLND and achieves meaningful pathologic responses. Survival is similar with <pT2N0 and pT0N0 post NAC pathology. Pts with post NAC ≥pT2, + margins, and + LN do poorly. Increasing LN yield on PLND contributes to OS.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11638-e11638
Author(s):  
C. Rodriguez Franco ◽  
D. Aguiar Bujanda ◽  
S. Saura Grau ◽  
U. Bohn Sarmiento ◽  
J. Aguiar Morales

e11638 Background: Male breast cancer (MBC) is a very uncommon illness relative to female breast cancer (FBC) The are some differences between both that could influence the management, like gene expression, hormonal enviroment and anatomy of the gland. Methods: Retrospective review of patients diagnosed in a seventeen year period (1990–2007). Results: There were 22 male patients diagnosed in our institution with a median age of 62.4 years (range 34 to 83 years) during the period. One had bilateral breast cancer. Stage of disease was I-II in 13 patients (59%), III in 8 patients (36%), and IV in 1 patient (5%). Five patients (22.7%) had familiar history of breast cancer and 3 patients (13%) had familiar history of other kind of neoplasias. Hormonal receptor were positive in thirteen patiens (59%) and 5 were unknown (23%). Ductal carcinoma was the predominant histologic subtype with 17 patients (77%). Other types were pleomorfic, mucoid and papilar carcinoma (one each type) and 3 patients with intrapapilar carcinoma with microinfiltration. Eleven of 20 patologic available axilla had node positive (55%). Grade were I in 3 patients (13%), II in 4 patients (18%), III in 8 (37%) and undefined in in 7 (32%). Surgery was the initial treatment in 18 patients (81%), just 2 of them performing tumorectomy and the other 16 radical mastectomy. 3 patients receive neoadyuvant chemotherapy with 1 complete response and one partial response. 13 patients (59%) received adjuvant radiotherapy (RT) and 17 (77%) adjuvant hormonal therapy (HT) mostly of them with tamoxifen (14/17) and the others 3 patients with aromatase inhibitors. Adjuvant chemotherapy was used in 9 (41%) patients with an antracycline regimen. With a median follow-up of 78 months (range 7–125), overall survival was 77 % with 3 patients died with progression disease and two patients died because of intercurrent illness without evidence of cancer progression. Regarding to our population area we had an incidence of 0.96/100.000 inhabitants during this 17 year period. Conclusions: MBC in our area are in the upper limit of occidental countries incidence. Most cases can be treated with radical intention with surgery (mostly radical) and adjuvant treatment with a good survival percentage. We manage MBC like we do FBC because of absence of clinical randomized trial specific for MBC. No significant financial relationships to disclose.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1502-1502
Author(s):  
Bhavana Sree Vangara Chapman ◽  
Diane D. Liu ◽  
Shane Richard Stecklein ◽  
Angelica Gutierrez Barrera ◽  
Wendy A. Woodward ◽  
...  

1502 Background: Women with germline mutations in DNA repair pathways are at an increased risk of developing breast cancer. We posit that tumors arising in these patients may be more sensitive to radiotherapy and, therefore, patients may experience improved locoregional control and survival outcomes following adjuvant radiotherapy as compared to patients without DNA repair pathway mutations. Methods: We evaluated the records of 2,221 women with stage 0-III de novo primary breast cancer treated with surgery and adjuvant radiotherapy who all underwent genetic testing at our institution from 1993 to 2018. Mutations were categorized as pathogenic variant, variant of unknown significance (VUS), or negative. The Kaplan-Meier method was used to estimate the locoregional recurrence rate (LRR), rate of distant metastasis (DM), disease-free survival (DSS), and overall survival (OS) from the time of surgery. Results: The median age at diagnosis was 45 years (range 19-84). Median follow-up time was 7 years (95% confidence interval 6.6-7.4). Among 1,960 patients with evaluable radiation records, 752 (38.4%) received breast only radiation, 12 (0.6%) received chest wall only radiation, and 1,196 (61.0%) received breast/chest wall and regional nodal radiation. A total of 255 (11.4%) and 162 (7.3%) patients had a pathogenic variant mutation and a VUS only, respectively. Pathogenic variant and VUS in BRCA1/2 mutations were detected in 216 (9.7%) and 82 (3.7%) patients, respectively. Perturbations in ATM, CHEK2, MLH, MSH2/6, MUTYH, PALB2, RAD50/51, and/or TP53 were detected in 71% (85/119) of patients who tested positive for a non- BRCA1/2 pathogenic variant or VUS. On univariate analysis, there was no significant association between BRCA1/2 mutation status or any genetic mutation and rate of LRR or DM, DSS, or OS ( p > 0.10 for all). Clinicopathological features including advanced stage and lymphovascular invasion were associated with higher cumulative incidence of LRR and DM as well as shorter DFS and OS ( p < 0.01 for all). Conclusions: Herein we report on the largest cohort of women with breast cancer treated with adjuvant radiotherapy at a single institution who have undergone germline testing. Our findings suggest that the overall prognosis of breast cancer treated with adjuvant radiotherapy in patients with germline BRCA1/2 or other genetic predisposition is similar to patients with sporadic breast cancer. Further investigation to evaluate acute or late toxicities and secondary cancers as a result of radiotherapy is warranted.


Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 738 ◽  
Author(s):  
Michal Vocka ◽  
Martina Zimovjanova ◽  
Zuzana Bielcikova ◽  
Petra Tesarova ◽  
Lubos Petruzelka ◽  
...  

Breast cancer (BC) prognosis in BRCA1 and BRCA2 mutation carriers has been reported contradictorily, and the significance of variables influencing prognosis in sporadic BC is not established in BC patients with hereditary BRCA1/BRCA2 mutations. In this retrospective cohort study, we analyzed the effect of clinicopathological characteristics on BC prognosis (disease-free survival [DFS] and disease-specific survival [DSS]) in hereditary BRCA1/BRCA2 mutation carriers. We enrolled 234 BRCA1/BRCA2 mutation carriers and 899 non-carriers, of whom 191 carriers and 680 non-carriers, with complete data, were available for survival analyses. We found that patients with ER-positive tumors developed disease recurrence 2.3-times more likely when they carried a BRCA1/BRCA2 mutation (23/60; 38.3% ER-positive carriers vs. 74/445; 16.6% ER-positive non-carriers; p < 0.001). ER-positive mutation carriers also had a 3.4-times higher risk of death due to BC compared with ER-positive non-carriers (13/60; 21.7% vs. 28/445; 6.3%; p < 0.001). Moreover, prognosis in ER-negative BRCA1/BRCA2 mutation carriers was comparable with that in ER-positive non-carriers. Our study demonstrates that ER-positivity worsens BC prognosis in BRCA1/BRCA2 mutation carriers, while prognosis for carriers with ER-negative tumors (including early-onset) is significantly better and comparable with that in ER-positive, older BC non-carriers. These observations indicate that BRCA1/BRCA2 mutation carriers with ER-positive BC represent high-risk patients.


2009 ◽  
Vol 32 (3) ◽  
pp. 250 ◽  
Author(s):  
Wen-sheng Qui ◽  
Lu Yue ◽  
Ai-ping Ding ◽  
Jian Sun ◽  
Yang Yao ◽  
...  

Purpose: To assess the prognostic value of co-expression of estrogen receptor (ER)-beta and human epidermal growth factor receptor 2 (HER2) in primary breast cancer patients in China. Methods: Tumour specimens from 308 patients undergoing surgery for primary breast cancer were evaluated. Expression of ER-beta and HER-2 was investigated by the immunohistochemistry. Results: 123 patients (40%) were ER-beta positive and 58 (18.5 %) were HER2 positive. Among the 58 HER2 positive patients, 44 were ER-beta positive and 14 were ER-beta negative. ER-beta positive was associated with HER2 positive (75.9%, P=0.018) as well as ER-alpha positive (79.7%, P=0.023), poor cell differentiation (77.2% grade 2 or 3, P=0.010) and menopause age < 45 yr (55.3%, P=0.031). HER2 positive was associated with poor cell differentiation (93.1%, P=0.001), ?3cm tumour size (67.2%, P=0.011). Conclusion: Both ER-beta positive and HER2 positive status was associated with poorer overall survival (OS) by univariate analysis. In both HER2 positive and HER2 negative subgroups, ER-beta positive was associated with poorer distant disease free survival (DDFS) but not OS, which implied that ER-beta might relate to metastasis in breast cancer.


2021 ◽  
Vol 22 (2) ◽  
pp. 889
Author(s):  
Ava Kwong ◽  
Cecilia Y. S. Ho ◽  
Vivian Y. Shin ◽  
Chun Hang Au ◽  
Tsun Leung Chan ◽  
...  

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.


Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2506
Author(s):  
Mark van Barele ◽  
Bernadette A. M. Heemskerk-Gerritsen ◽  
Yvonne V. Louwers ◽  
Mijntje B. Vastbinder ◽  
John W. M. Martens ◽  
...  

Triple-negative breast cancers (TNBC) occur more frequently in younger women and do not express estrogen receptor (ER) nor progesterone receptor (PR), and are therefore often considered hormone-insensitive. Treatment of premenopausal TNBC patients almost always includes chemotherapy, which may lead to premature ovarian insufficiency (POI) and can severely impact quality of life. Hormone replacement therapy (HRT) is contraindicated for patients with a history of hormone-sensitive breast cancer, but the data on safety for TNBC patients is inconclusive, with a few randomized trials showing increased risk-ratios with wide confidence intervals for recurrence after HRT. Here, we review the literature on alternative pathways from the classical ER/PR. We find that for both estrogens and progestogens, potential alternatives exist for exerting their effects on TNBC, ranging from receptor conversion, to alternative receptors capable of binding estrogens, as well as paracrine pathways, such as RANK/RANKL, which can cause progestogens to indirectly stimulate growth and metastasis of TNBC. Finally, HRT may also influence other hormones, such as androgens, and their effects on TNBCs expressing androgen receptors (AR). Concluding, the assumption that TNBC is completely hormone-insensitive is incorrect. However, the direction of the effects of the alternative pathways is not always clear, and will need to be investigated further.


Open Heart ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. e001526
Author(s):  
Elena Tessitore ◽  
David Carballo ◽  
Antoine Poncet ◽  
Nils Perrin ◽  
Cedric Follonier ◽  
...  

ObjectiveHistory of cardiovascular diseases (CVDs) may influence the prognosis of patients hospitalised for COVID-19. We investigated whether patients with previous CVD have increased risk of death and major adverse cardiovascular event (MACE) when hospitalised for COVID-19.MethodsWe included 839 patients with COVID-19 hospitalised at the University Hospitals of Geneva. Demographic characteristics, medical history, laboratory values, ECG at admission and medications at admission were collected based on electronic medical records. The primary outcome was a composite of in-hospital mortality or MACE.ResultsMedian age was 67 years, 453 (54%) were males and 277 (33%) had history of CVD. In total, 152 (18%) died and 687 (82%) were discharged, including 72 (9%) who survived a MACE. Patients with previous CVD were more at risk of composite outcomes 141/277 (51%) compared with those without CVD 83/562 (15%) (OR=6.0 (95% CI 4.3 to 8.4), p<0.001). Multivariate analyses showed that history of CVD remained an independent risk factor of in-hospital death or MACE (OR=2.4; (95% CI 1.6 to 3.5)), as did age (OR for a 10-year increase=2.2 (95% CI 1.9 to 2.6)), male gender (OR=1.6 (95% CI 1.1 to 2.3)), chronic obstructive pulmonary disease (OR=2.1 (95% CI 1.0 to 4.2)) and lung infiltration associated with COVID-19 at CT scan (OR=1.9 (95% CI 1.2 to 3.0)). History of CVD (OR=2.9 (95% CI 1.7 to 5)), age (OR=2.5 (95% CI 2.0 to 3.2)), male gender (OR=1.6 (95% CI 0.98 to 2.6)) and elevated C reactive protein (CRP) levels on admission (OR for a 10 mg/L increase=1.1 (95% CI 1.1 to 1.2)) were independent risk factors for mortality.ConclusionHistory of CVD is associated with higher in-hospital mortality and MACE in hospitalised patients with COVID-19. Other factors associated with higher in-hospital mortality are older age, male sex and elevated CRP on admission.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jose G. Bazan ◽  
Sachin R. Jhawar ◽  
Daniel Stover ◽  
Ko Un Park ◽  
Sasha Beyer ◽  
...  

AbstractIn the modern era, highly effective anti-HER2 therapy is associated with low local-regional recurrence (LRR) rates for early-stage HER2+ breast cancer raising the question of whether local therapy de-escalation by radiation omission is possible in patients with small-node negative tumors treated with lumpectomy. To evaluate existing data on radiation omission, we used the National Cancer Database (NCDB) to test the hypothesis that RT omission results in equivalent overall survival (OS) in stage 1 (T1N0) HER2+ breast cancer. We excluded patients that received neoadjuvant systemic therapy. We stratified the cohort by receipt of adjuvant radiation. We identified 6897 patients (6388 RT; 509 no RT). Patients that did not receive radiation tended to be ≥70 years-old (odds ratio [OR] = 3.69, 95% CI: 3.02–4.51, p < 0.0001), to have ≥1 comorbidity (OR = 1.33, 95% CI: 1.06–1.68, p = 0.0154), to be Hispanic (OR = 1.49, 95% CI: 1.00–2.22, p = 0.049), and to live in lower income areas (OR = 1.32, 95% CI: 1.07–1.64, p = 0.0266). Radiation omission was associated with a 3.67-fold (95% CI: 2.23–6.02, p < 0.0001) increased risk of death. While other selection biases that influence radiation omission likely persist, these data should give caution to radiation omission in T1N0 HER2+ breast cancer.


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