scholarly journals Effects of BRCA Germline Mutations on Triple-Negative Breast Cancer Prognosis

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Katarzyna Pogoda ◽  
Anna Niwińska ◽  
Elżbieta Sarnowska ◽  
Dorota Nowakowska ◽  
Agnieszka Jagiełło-Gruszfeld ◽  
...  

Germline BRCA1 and BRCA2 mutations confer an increased lifetime risk for breast cancer and ovarian cancer. Several studies have investigated prognosis among BRCA1/2 mutation carriers and noncarriers, but the prognostic impact on outcomes of breast cancer patients has not been determined. The aim of this study was to determine the prognosis of TNBC patients with and without BRCA1/2 germline mutation. Among 502 patients diagnosed with TNBC between 2005 and 2008, 124 patients with a strong family history of breast cancer or ovarian cancer as well as TNBC patients diagnosed under 45 years were referred to the Genetic Counseling Unit for genetic counselling and genetic tests. In 30 (24%) of them, the BRCA1/2 mutation was detected (the most common 5382insC in 18 (60%) patients). The median follow-up of the entire group was 60 months. BRCA1/2 mutation carriers were statistically significantly younger at TNBC diagnosis compared with nonmutation patients (41 vs 47 years, respectively). Patients with the BRCA1/2 mutation had smaller tumors (stage I: 47% vs 24.5% in noncarriers), but there was no significant difference in the regional nodal status (58.5–63% with cN0). Contralateral breast cancer developed in 26.5% of BRCA1/2 mutation carriers and in 14% of noncarriers. Other primary cancers were also slightly more common in BRCA1/2 mutation carriers (16.5% vs 9.5%). The performed analysis did not show any significant differences between the groups in recurrence-free survival (p=0.312). There was no significant difference between patients with or without BRCA1/2 mutation as regards overall survival (p=0.649) and the risk of TNBC death (p=0.333). The survival from detection of metastases was similar in two groups (p=0.865). Our study demonstrated that the BRCA1 mutation does not affect TNBC patients’ outcomes.

2020 ◽  
Vol 8 (11) ◽  
pp. 656-660
Author(s):  
Anjali Vinocha ◽  

Introduction:Breast cancer is the most common cancer in women, with 5- and 10-year relative survival rates are 91% and 84%, respectively for women with invasive breast cancer. This study aimed to detect the role of serum breast cancer marker CA 15-3 for early detection of metastasis, relapse or recurrence for management of breast cancer patients. Methods: It was a retrospective cohort study with a total of 132 breast cancer patients from the year 2010 to march 2020 were taken and followed up. For these patients demographic, biochemical parameters, radiological and clico-pathological data were collected and analysed. Result: The mean age at the time of presentation and mean duration of follow-up was 47 years and 31 months respectively. There was elevation in the serum level of CA 15-3 at the time of diagnosis of metastasis, recurrence or residual disease in 41 patients. This shows that sensitivity of elevated CA 15-3 (> 30 IU/ml) level in Ca Breast patients was 84%, 75 % and 75 % with respect to metastasis, recurrence and relapse. Log Rank test Chi- square value was 7.39 which was statistically significant (p=0.007). Cox proportional hazard model was created for effect of age at presentation, CA 15-3 at the time of diagnosis and MRM on distant metastasis and was statistically significant (p=0.037). Conclusion: We recommend that for the management of breast cancer patients, Cancer antigen (CA 15-3) levels can be used as prognostic marker for early diagnosis of metastasis, recurrence or relapse.


1995 ◽  
Vol 13 (11) ◽  
pp. 2712-2721 ◽  
Author(s):  
M R Sertoli ◽  
P Bruzzi ◽  
P Pronzato ◽  
P Queirolo ◽  
D Amoroso ◽  
...  

PURPOSE The aim of this multicentric randomized trial was to determine whether reducing the interval between surgery and chemotherapy improves the outcome of breast cancer patients. PATIENTS AND METHODS Between June 1985 and July 1992, 600 breast cancer patients, clinical stages T1-3A,N0-2,M0 were randomly assigned to a perioperative cycle (PC) of cyclophosphamide 600 mg/m2, epidoxorubicin 60 mg/m2, and fluorouracil 600 mg/m2 (CEF). Node-negative (N-) patients did not receive any further treatment. Node positive (N+) patients received 11 cycles if previously given PC, or 12 cycles of CEF alternated with cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2 (CMF). In addition, N+ patients received concomitant or sequential 5-year tamoxifen therapy. RESULTS At a median follow-up duration of 5.7 years, no significant difference in survival (88% v 84%, P = .3) between the two treatment arms was seen. However, a difference of borderline significance in relapse-free survival (RFS; 76% v 70%, P = .053) was evident. A significant survival advantage for the PC arm was detected only in the estrogen receptor-negative (ER-) patients (P = .003). RFS was significantly improved in N- patients, postmenopausal patients, and ER- patients. Multivariate analyses show that pathologic tumor size, nodal status, receptor status, and treatment (only in ER- patients) are significantly correlated with survival and RFS. PC toxicity did not influence wound healing. CONCLUSION This study provides preliminary evidence that PC positively affects relapse rate and survival in some subgroups, namely, ER- patients.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 523-523 ◽  
Author(s):  
M. Y. Halyard ◽  
T. M. Pisansky ◽  
L. J. Solin ◽  
L. B. Marks ◽  
L. J. Pierce ◽  
...  

523 Background: Adjuvant trastuzumab (Herceptin [H]) with chemotherapy improves outcome in HER2+ breast cancer (BC). Preclinical studies suggest H may enhance RT. We herein assess if H given with adjuvant RT increases adverse events (AE) after breast conserving surgery or mastectomy. Methods: N9831 randomized 3505 women with pT1–3N1–2M0, pT2–3N0M0, or pT1cN0M0 (ER/PR negative) HER2+ BC to doxorubicin (A) and cyclophosphamide (C) followed by weekly paclitaxel (T), AC→T→H, or AC→TH→H. Post-lumpectomy breast ± nodal RT was recommended, as was post-mastectomy chest wall + nodal RT (>3 nodes +); internal mammary RT was prohibited. RT started within 5 weeks of completion of T and allowed concurrently with H. 2324 eligible patients were enrolled on study prior to April 25, 2004: 1460 patients receiving RT are available for analysis of RT-associated AEs. Also, 1286 patients on +H arms who completed T (908 +RT and 378 -RT) are available for analysis of clinical cardiac events (CE). Rates of RT-associated AEs were compared across treatment arms, and rates of CE were compared for +RT vs -RT patients within +H arms. All reported p-values are for chi-squared statistics. Results: With a median follow-up of 1.5 years, significant differences among arms in RT-associated AEs were not identified. No significant differences across arms in +RT patients existed in the incidence of skin reaction (p=0.78), pneumonitis (p=0.78), dyspnea (p=0.87), cough (p=0.54), esophageal dysphagia (p=0.26), or neutropenia (p=0.16). There was a significant difference in +RT patients in the incidence of leukopenia (p=0.02) with higher incidence rates in the arms receiving H. RT did not increase the frequency of CE. In the AC→T→H arm, the incidence of CE was 2.2% in +RT patients versus 2.9% in -RT patients. In the AC→TH→H arm, the incidence of CE was 1.5% in +RT patients versus 6.3% in -RT patients. No difference in CE was seen between left- and right-sided RT fields in +RT patients in either +H arm. Conclusion: Concurrent administration of adjuvant RT with H in early stage breast cancer patients is not associated with an increased incidence of acute RT AEs. Further follow-up is required to assess late AEs. No significant financial relationships to disclose.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1000-1000 ◽  
Author(s):  
Thomas B. Julian ◽  
Stewart J. Anderson ◽  
David N. Krag ◽  
Seth P. Harlow ◽  
Joseph P. Costantino ◽  
...  

1000 Background: NSABP B-32, the largest surgical prospective randomized phase III trial was designed to compare overall survival (OS), disease-free survival (DFS), and morbidity between SNR alone vs SNR + AD in SN negative (-) pts. We present 10 yr outcome data for primary endpoints as well as updated data on the effect of occult metastases, found later in the SN by central, detailed pathologic analysis. Methods: 5,611 women with operable, clinically N0, invasive breast cancer were randomized to SNR + AD (Group [Grp] 1) or to SNR alone with AD only if SNs were positive (Grp2). 3,989 (71.1%) of 5,611 pts were SN-. 3,986 (99.9%) of these SN- pts had follow-up information: Grp 1: 1,975, Grp 2:2,011. Median time on study was 9.4 yrs. Cox proportional hazard models adjusting for study stratification variables were used to compare OS and DFS between the two groups. Two-sided p values were used. HR values > 1 indicate a more favorable outcome in Grp 1 Results: At 10 yrs, there continues to be no significant difference in OS between the two groups (HR: 1.11, p = 0.27). 10 yr Kaplan-Meier (K-M) estimates for OS are 87.8% for SNR alone and 88.9% for SNR + AD. There continues to be no significant difference in DFS between the two groups (HR: 1.01, p=0.92). 10-yr K-M estimates for DFS were 76.9% for both groups. Occult nodal disease was originally detected in 3,884 pts (15.8%) with SN- on initial H and E analysis. Comparisons between the groups with and without occult disease yielded an adjusted HR for OS: 1.25 (p = 0.08) with an absolute difference at 10 yrs of 2.8% and a HR for DFS: 1.24 (p = 0.018) with an absolute difference of 4.1%. The cumulative incidences of local-regional events were low (10-yr values: SNR 4.0%, SNR+AD, 4.3%) and not significant (HR: 0.95, p = 0.77). Conclusions: At 10 yrs there continues to be no significant differences in OS and DFS between SNR and SNR + AD in pts with negative SN. The relative increase in risk of DFS and OS for pts with occult SN metastases remains stable. Support: PHS grants: NSABP: U10CA-12027, U10CA-37377, U10CA-69651, U10CA-69974; VT Ca Cntr: P30 CA22435; DNK: 5RO1CA074137 NCI Dpt HHS. Clinical trial information: NCT00003830.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21702-e21702
Author(s):  
David Azoulay ◽  
Anca Leibovici ◽  
Rivka Sharoni ◽  
Hadassah Goldberg

e21702 Background: We previously published preliminary results suggesting an association between the met-BDNF allele and vulnerability to paclitaxel-induced peripheral neuropathy (PIPN) in breast cancer patients. Here we present updated data obtained from our extended study. Methods: 35 patients; 34 women (33 with breast cancer and 1 with ovarian cancer) and one man (breast cancer) completed their follow-up. Peripheral neuropathy (PN) was assessed at diagnosis and along the treatment protocol, using the reduced version of Total Neuropathy Score (TNSr). Patients with TNSr≥2 at diagnosis were determined with pre-existing PN (Pre-PN). Allelic discrimination of BDNF polymorphism (rs6265) was determined by Sanger sequencing. Results: BDNF genotype Val/Val was found in 20 patients (57.14%), Val/Met in 15 patients (42.86%). No patient had the Met/Met genotype. 10 patients (28.57%) were diagnosed with Pre-PN, 3 of them with diabetic-related neuropathy. A higher incidences of the Met-BDNF allele was found in patients with Pre-PN as compared to patients with no Pre-PN (7/10 (70%) vs. 8/25 (32%) Val/Met in Pre-PN and no Pre-PN respectively, prob > ChiSq < 0.05). The three patients with diabetic related Pre-PN were genotyped Met-BDNF. The maximal TNSr scores developed by each patient during follow-up were higher in Met-BDNF patients compare to Val/Val patients. (Maximal TNSr mean ± SEM in Val/Val 4.80±0.62 vs. 7.73±1.34 in Val/Met BDNF, prob < t 0.04). No difference in the maximal TNSr scores between Met-BDNF and Val/Val patients were shown after excluding the patients with Pre-PN (Maximal TNSr mean ± SEM in Val/Val 5.05±0.78 vs. 5.25±0.62 in Val/Met BDNF, prob < t 0.44). Conclusions: Our data demonstrate an association between met-BDNF and Pre-PN. Higher maximal TNSr scores in our met-BDNF patients is generally the consequence of their higher Pre-PN.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 580-580 ◽  
Author(s):  
Xavier Pivot ◽  
Mark D. Pegram ◽  
Javier Cortes ◽  
Diana Lüftner ◽  
Gary H. Lyman ◽  
...  

580 Background: SB3 is an approved biosimilar of reference trastuzumab (TRZ). At additional 2-year follow-up after completing neoadjuvant and adjuvant treatment, there was a difference in event-free survival (EFS), but no difference in overall survival (OS) between SB3 and TRZ. Upon monitoring quality attributes of TRZ, a marked downward shift in antibody-dependent cell-mediated cytotoxicity activities (ADCC) was observed in TRZ lots with expiry dates from Aug 2018 to Dec 2019. Some of the lots were used in the Phase III study. This is a post-hoc analysis of EFS and OS by ADCC status from a 3-year follow-up to investigate the difference in EFS between SB3 and TRZ. Methods: After completion of neoadjuvant and adjuvant therapy in patients with HER2 positive early breast cancer, patients from selected countries participated in a 5-year follow-up study (NCT02771795). Within the TRZ group, patients exposed to at least one shifted ADCC lot and those never exposed to shifted ADCC lot during neoadjuvant period were considered as “Exposed” and “Unexposed,” respectively. EFS and OS after 3-year follow-up was analyzed by ADCC status in the long-term follow-up set. Results: 367 patients (SB3, N = 186; TRZ, N = 181) were enrolled in the follow-up study. Within TRZ, 55 patients were Unexposed and 126 patients were Exposed. At a median follow-up duration of 40.8 months in SB3 and 40.5 months in TRZ, 3-year EFS rates were 92.5% in SB3, 94.5% in Unexposed, and 82.5% in Exposed and OS rates were 97.0%, 100%, and 90.6%, respectively. Exposed was associated with decreased EFS compared to Unexposed (HR 0.14, 95% CI 0.04-0.51, p= 0.003). There was a trend of decreased OS in Exposed compared to Unexposed, however, there was no significant difference (HR 0.14, 95% CI 0.02-1.15, p= 0.068). Between SB3 and Unexposed, no difference was observed in EFS (HR 1.06, 95% CI 0.33-3.44, p= 0.923), or OS (HR 0.54, 95% CI 0.05-5.44, p= 0.600). Conclusions: Within the TRZ group, Exposed showed significantly lower EFS compared to Unexposed, and a similar trend was observed in OS with no statistical significance. Between SB3 and Unexposed, no significant difference in EFS or OS was observed. Clinical trial information: NCT02771795.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12118-e12118
Author(s):  
Meng Xiu ◽  
Pin Zhang

e12118 Background: HR-/HER2+ breast cancer is a subtype with aggressive characteristic and poor survival. More clinical evidence are needed for choice of therapeutic strategies. Methods: Patients with T1-3N0-3M0 received preoperative chemotherapy (PTX 175 mg/m2, CBP AUC 4, q2w*6) combined with trastuzumab (2mg/kg qw) or standard postoperative chemotherapy such as ddAC-PH, AC-PH, TCH. The primary endpoint was RFS. Results: 86 patients were enrolled, 43 received preoperative chemotherapy (pre arm) and the other 43 received postoperative chemotherapy (post arm). There was no significant difference in baseline between the two arms. 22.1% of patients were stage IIA, 25.6% IIB, 34.9% IIIA, and 18.6% IIIC. At a median follow-up of 33.4 months, 16 patients had relapsed (pre arm 8, post arm 8). The median time from diagnosis to relapse was 22.8 months (7.1-49.2) and 23.8 months (11.4-37.4) in pre and post arm. Kaplan-Meier survival analysis estimated that the 3-year RFS were similar (pre vs post: 73.4% vs 75.4%, p= 0.631). Only 1 death occurred in post arm. Table showed that in subgroups, there was no statistical difference in risk of recurrence between pre and post arms. In pre arm, ORR was 97.7% clinically, and pCR (ypT0/TisN0) was 39.0%. No patients achieved pCR relapsed, and the residual invasive lesions indicated poor prognosis. Table showed that Neo-Bioscore 4-5 was related to recurrence event significantly ( p= 0.021). The rate of breast-conserving in pre arm was higher (19.5% vs 9.3%), and PCb regiments every 2 weeks had similar adverse effects with standard chemotherapy, and less patients had dose reductions (18.6% vs 25.6%). Conclusions: Preoperative chemotherapy versus standard postoperative chemotherapy results in similar RFS among HR-/HER2+ patients. Preoperative chemotherapy can identify prognosis of patients early by Neo-Bioscore and adjuvant therapy should be strengthened for high-risk patients. PCb every 2 weeks combined with trastuzumab can be an option of preoperative therapy for HER2+ breast cancer. Clinical trial information: NCT02934828. [Table: see text]


2006 ◽  
Vol 24 (16) ◽  
pp. 2437-2443 ◽  
Author(s):  
Lori J. Pierce ◽  
Albert M. Levin ◽  
Timothy R. Rebbeck ◽  
Merav A. Ben-David ◽  
Eitan Friedman ◽  
...  

Purpose We compared the outcome of breast-conserving surgery and radiotherapy in BRCA1/2 mutation carriers with breast cancer versus that of matched sporadic controls. Methods A total of 160 BRCA1/2 mutation carriers with breast cancer were matched with 445 controls with sporadic breast cancer. Primary end points were rates of in-breast tumor recurrence (IBTR) and contralateral breast cancers (CBCs). Median follow-up was 7.9 years for mutation carriers and 6.7 years for controls. Results There was no significant difference in IBTR overall between carriers and controls; 10- and 15-year estimates were 12% and 24% for carriers and 9% and 17% for controls, respectively (hazard ratio [HR], 1.37; P = .19). Multivariate analyses for IBTR found BRCA1/2 mutation status to be an independent predictor of IBTR when carriers who had undergone oophorectomy were removed from analysis (HR, 1.99; P = .04); the incidence of IBTR in carriers who had undergone oophorectomy was not significantly different from that in sporadic controls (P = .37). CBCs were significantly greater in carriers versus controls, with 10- and 15-year estimates of 26% and 39% for carriers and 3% and 7% for controls, respectively (HR, 10.43; P < .0001). Tamoxifen use significantly reduced risk of CBCs in mutation carriers (HR, 0.31; P = .05). Conclusion IBTR risk at 10 years is similar in BRCA1/2 carriers treated with breast conservation surgery who undergo oophorectomy versus sporadic controls. As expected, CBCs are significantly increased in carriers. Although the incidence of CBCs was significantly reduced in mutation carriers who received tamoxifen, this rate remained significantly greater than in controls. Additional strategies are needed to reduce contralateral cancers in these high-risk women.


2015 ◽  
Vol 6 (1) ◽  
pp. 27-32
Author(s):  
Hanan R. Nassar ◽  
Alfred E. Namour ◽  
Hanan E. Shafik ◽  
Amr S. El Sayed ◽  
Samar M. Kamel ◽  
...  

Abstract Many studies have demonstrated that osteopontin (OPN) contributes functionally to aggressive behaviour in many tumours including breast cancer. This study aims to investigate its role as a simple biochemical marker easily measured in plasma of breast cancer patients to give an early signal for metastases and to detect its relationship to clinicopathological findings and survival. We measured plasma OPN, CA15.3 and serum alkaline phosphatase (ALP) activity in 55 patients, 28 with early stage breast cancer and 27 with bone metastasis out of whom 20 had metastasis in other sites. The median age at diagnosis for non-metastatic cases was 60 years (range 35-85) and for metastatic cases was 45.5 years (range 32-59). In the non-metastatic group, 78.57% of the patients were histologically graded as grades I and II and 21.43% as grade III tumours. In the metastatic group, 81.48% of the patients had grades I and II and 18.52% had grade III tumours; 54% of patients in the non-metastatic group were at stage II and 46% were at stage III at presentation. All patients of group II had bone metastasis, 33% had liver metastases, 25.9% had lung metastasis and 14.8% had lymph node metastasis. Patients with non-metastatic disease had a median OPN level of 55 ng/ml (range 54-150 ng/l), while those in the metastatic group had a median of 148.0 ng/l (range 56.0-156.0 ng/l), a difference which was statistically significant (P = 0.001). There was no statistically significant difference in the median levels of CA15.3 and ALP between both groups. The median OPN level was significantly higher with serum ALP level above 90, progesterone receptor (PR) status, bone and visceral metastasis. Median OPN was not affected significantly by menopausal status (P-value 0.3), tumour grade (P-value 0.3), estrogen receptor (ER) status (P-value 0.7), pathological type (P-value 0.42) or serum CA15.3 level (P-value 0.6). At the end of 12-year follow-up, 83% of the patients survived (92.3% in the non-metastatic versus 74.1% in the metastatic group). The estimated median survival for the whole study population at 12 years was 13 years (95% CI 8.144-17.856). The estimated median survival was 13 years (95% CI 0) and 12 years (95% CI 4.893-19.11) in patients with median OPN levels of <142 and ≥142, respectively, a difference which was not statistically significant (P = 0.343). No statistically significant difference in overall survival OS was noticed in relation to menopausal status (P = 0.7), pathological type (P = 0.4) and hormone receptor status (P = 0.3). At 6-year follow-up, it was found that OS was affected by the presence of visceral metastasis, tumour grade, serum plasma level of ALP and the serum level of CA15.3 (P = 0.0006, 0.007, 0.001 and 0.03, respectively). However, the presence of bone metastasis did not affect OS (P = 0.6). Osteopontin level can be a simple biochemical marker easily measured in plasma of breast cancer patients to give early signals for metastases, but not a prognostic factor for survival.


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