Survival Analysis of Breast Cancer in Patients with HER2/neu+, ER-, PR-: a Retrospective Cohort Study

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Aim: We aimed to study the characteristics of the breast cancer patients with positive HER2/neu+, ER- and PR- receptors. Methods: 119 patients with breast cancer were included in this retrospective cohort study from 2006 to 2016. The overall and disease-free survival were evaluated. Results: Most prevalent type of tumor was IDC, grade III cancer and stage II. Recurrence/metastasis occurred in 18.49%. Most common sites of metastasis were lungs and liver. Total mortality rate was 10.92%. Overall and disease-free survival times were 40.04 and 22.29 months, respectively. The median survival time was about 118 months. Conclusion: Breast cancers with positive HER2/neu and negative estrogen and progesterone receptors had low overall and disease-free survival rates compared with ER+/PR+/HER2- tumors.

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Identification of Candidate Polymorphisms on Stress Oxidative and DNA Damage Repair Genes Related with Clinical Outcome in Breast Cancer Patients
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  • International Journal of Molecular Sciences
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The Clinicopathological Factors Associated with Disease Progression in Luminal A Breast Cancer and Characteristics of Metastasis: A Retrospective Study from A Single Center in China.
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Abstract PD10-06: Clinical behavior and outcomes of BRCA-mutated breast cancer in young patients according to type of BRCA mutation and hormone receptor status: Results from an international cohort study
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Background: Young breast cancer patients (pts) carrying a germline BRCA mutation (mBRCA) have similar outcomes as non-carriers. However, there is currently lack of evidence regarding the impact of mBRCA type and hormone receptor status on clinical behavior and outcomes of mBRCA breast cancer. We aim to address these questions in the largest dataset to date of young mBRCA breast cancer pts. Methods: This was an international, multicenter, hospital-based, retrospective cohort study. Women harboring deleterious germline mBRCA1 or mBRCA2 that received a diagnosis of stage I-III invasive early breast cancer at age ≤40 years between January 2000 and December 2012 were included. Baseline pts, tumor, and treatment characteristics, pattern and risk over time of disease-free survival (DFS) events, and survival outcomes (DFS, distant recurrence-free interval [DRFI] and overall survival [OS]) were compared between mBRCA1 and mBRCA2 pts overall and by hormone receptor status. Multivariate Cox proportional hazard models were used to compare hazard rates (HRs). Results: 1,236 young mBRCA breast cancer pts were included. Among 808 and 428 pts with mBRCA1 or mBRCA2, respectively, 191 (23.6%) and 356 (83.2%) had hormone receptor-positive tumors while 617 (76.4%) and 72 (16.8%) hormone receptor-negative disease (p<0.001). Compared to mBRCA2 breast cancer pts, those with mBRCA1 were younger, more likely to have reported Jewish ancestry, had more grade 3 tumors, less nodal involvement, lobular histology and HER2 positivity, and received more frequently chemotherapy (all p<0.001). More mBRCA1 pts with hormone receptor-positive tumors did not receive adjuvant endocrine therapy (14.7% vs. 4.2%, p<0.001). No difference between mBRCA1 and mBRCA2 pts was observed in risk-reducing mastectomy (43.9% vs. 46.0%; p=0.371) or salpingo-oophorectomy (48.3% vs. 48.8%; p=1.0). Median follow-up was 7.9 years (range 5.6-10.6 years). Second primary breast cancers (17.0% vs. 12.2%, p=0.025) and non-breast primary malignancies (4.3% vs. 1.9%, p=0.033) were more frequent among mBRCA1 pts compared to mBRCA2 pts, while distant recurrences were less frequent (10.4% vs. 15.4%, p=0.013). 8-year DFS was 62.8% and 65.9% for mBRCA1 and mBRCA2 pts, respectively (adjusted HR 0.76; 95% CI 0.60-0.96). The worse DFS in mBRCA1 was observed regardless of hormone receptor status (pinteraction=0.848): hormone receptor-positive (adjusted HR 0.77; 95% CI 0.58-1.03) and hormone receptor-negative (adjusted HR 0.73; 95% CI 0.48-1.13). No differences in DRFI and OS were observed between mBRCA1 and mBRCA2 pts. Compared to pts with hormone receptor-negative disease, those with hormone receptor-positive breast cancer had higher chances of developing distant (± loco-regional) recurrences (16.1% vs. 9.0%; p<0.001) and less frequent second primary malignancies (BC: 12.1% vs. 17.9%, p=0.005; non-BC: 2.8% vs. 4.0%, p=0.216). No differences in DFS and OS were observed between pts with hormone receptor-positive or negative breast cancer. However, there was a trend towards worse DRFI in women with hormone receptor-positive breast cancer as compared to those with hormone receptor-negative disease (8-year DRFI: 83.4% vs. 90.1%; adjusted HR 1.39; 95% CI 0.94-2.05). Conclusions: In this large unique dataset, young mBRCA1 breast cancer pts had worse DFS than those with mBRCA2 mostly due to higher rates of second primary malignancies. Hormone receptor positivity had no positive prognostic value in young mBRCA breast cancer pts with a trend towards worse DRFI in those with hormone receptor-negative disease. These results provide important information for counseling young mBRCA breast cancer pts regarding treatment, prevention and follow-up care strategies. Citation Format: Matteo Lambertini, Marcello Ceppi, Anne-Sophie Hamy, Olivier Caron, Philip D. Poorvu, Estela Carrasco, Albert Grinshpun, Kevin Punie, Christine Rousset-Jablonski, Alberta Ferrari, Shani Paluch-Shimon, Angela Toss, Claire Senechal, Fabio Puglisi, Katarzyna Pogoda, Jose Alejandro Pérez-Fidalgo, Laura De Marchis, Riccardo Ponzone, Luca Livraghi, Maria Del Pilar Estevez-Diz, Cynthia Villarreal-Garza, Maria Vittoria Dieci, Florian Clatot, Francois P. Duhoux, Rossella Graffeo, Luis Teixeira, Octavi Córdoba, Amir Sonnenblick, Arlindo R. Ferreira, Ann H. Partridge, Antonio Di Meglio, Claire Saule, Fedro A. Peccatori, Marco Bruzzone, Lucia Del Mastro, Lieveke Ameye, Judith Balmaña, Hatem A. Azim, Jr. Clinical behavior and outcomes of BRCA-mutated breast cancer in young patients according to type of BRCA mutation and hormone receptor status: Results from an international cohort study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD10-06.

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  • Molecular Cancer Research
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Progesterone Receptors, Pathological Complete Response and Early Outcome for Locally Advanced Breast Cancer - a Single Centre Study. (PPLB - 01).
  • Apr 23, 2016
  • Indian Journal of Surgical Oncology
  • Sanjit Agrawal + 6 more

Neoadjuvant chemotherapy (NACT) for locally advanced breast cancer (LABC), apart from increasing breast conservation rates, also provides an opportunity to assess tumour response to chemotherapy, with Pathological Complete Response (pCR) described as an independent prognostic factor and a surrogate marker for better outcome and survival. Our primary aim was to identify clinical and pathological factors associated with pCR following NACT in patients with LABC treated at our institution. Our secondary aim was to analyze the impact of pCR and associated factors on disease free survival (DFS) and overall survival (OS). A retrospective analysis of LABC patients treated with NACT between Jun 2011 and Dec 2013. Clinical and histological variables were analyzed for association with pCR (no invasive or in situ carcinoma in breast or axillary lymph nodes). Kaplan-Meier curves and Cox regression model was used for survival analysis. All values were twosided, and statistical significance was defined as p<0.05. 240 patients were included. The median tumor size was 6cm, with T4 disease in 49.8%. 45% of tumors were of low grade (G1+G2) and 53.8% of high grade (G3). Estrogen Receptor (ER) was positive in 70.8%, progesterone receptor (PR) in 53.3% and Her2 in 38.8%. The preferred NACT regimen was sequential anthracycline and taxane and 88.8% of patients received this regimen. Of 93 potential Her2 Positive patients, only 23 received trastuzumab. Overall 23.2% patients had pCR. At median follow up of 21months (range, 3-42), 16.3% of patients had recurrent disease, and 6.7% had died. High tumor grade (p=0.04), PR negative status (p<0.01) and trastuzumab treatment (p=0.01) were significant predictors of pCR in univariate analysis. On multivariate analysis PR negativity (OR 3.2, 95% CI=1.6 to 6.04, p=0.001) and Trastuzumab use (OR 0.24, 95% CI=0.1 to 0.6, p=0.004) were significant. Patients with pCR had positive associations with survival (p<.02,OS& .02,DFS) and interestingly PR positivity had positive association with DFS (p=0.02) in Kaplan-Meier curves. On Cox regression, PR positivity (HR=0.3, p<0.01) and pCR (HR=0.2, p<0.01) correlated with DFS, though not with early OS. for the PR positive patients were paradoxical. Though less likely to have pCR (15%, vs 32% if PR negative), they had better DFS (p=0.02), and achieving pCR had no survival benefit in this group. In contrast, PR negative patients, irrespective of ER status, had a high pCR rate, and achieving pCR had survival advantage (p<0.05,DFS& p<0.02,OS). PR negative patients without pCR had the worst DFS (p<0.01) among all. High grade and Trastuzumab treatment as predictors of pCR, and pCR as a surrogate marker for survival are well recognized, and are supported by our findings. In present cohort, PR negativity showed prognostic importance independent of ER status. However these results were derived from sub-group, post-hoc analysis of data from a pre-existing cohort, without 'a-priori' hypothesis for survival analysis in relation to PR. These "hypothesis generating" results need confirmation by a well-designed prospective cohort or a randomized trial.

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  • 10.3760/cma.j.issn.0253-3766.2010.07.010
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  • Chinese journal of oncology
  • Yue-Ping Liu + 7 more

To evaluate the prognostic value of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her-2) in node-positive breast cancer patients treated by mastectomy. The clinicopathological data of 835 breast cancer patients treated by mastectomy from January 2000 to December 2004 were retrospectively analyzed. All had positive axillary nodes without distant metastases and with the immunohistochemistry staining of ER, PR and Her-2 available. 764 (91.5%) patients received anthracycline- and/or taxanes-based chemotherapy. 464 (55.6%) patients received hormonal therapy. Eight (1%) patients received trastuzumab. Postmastectomy radiotherapy were given to 352 out of 437(80.5%)patients with T3-T4 and/or N2-N3 disease and 68 out of 398(20.9%)patients with T1-2N1 disease. Patients were classified into 4 subgroups according to the status of hormone receptors (ER and PR, Rec) and Her-2: Rec(-)/Her-2(-) (triple negative), Rec(-)/Her-2(+), Rec(+)/Her-2(+) and Rec(+)/Her-2(-). End points were isolated locoregional recurrence (LRR), distant metastases (DM), disease-free survival (DFS) and overall survival (OS). 141 (16.9%) patients were Rec(-)/Her-2(-), 99 (11.9%) Rec(-)/Her-2(+), 157 (18.8%) Rec(+)/Her-2(+) and 438 (52.5%) Rec(+)/Her-2(-). Patients with Rec(+)/Her-2(-) breast cancer had a significantly lower 5-year LRR rate than others (6.2% vs. 12.9%, P = 0.004). Compared with patients with Rec(+) breast cancer, patients with Rec(-) breast cancer had significantly higher 5-year DM rate (26.4% vs. 19.7%, P = 0.0008), lower DFS rate (66.7% vs. 75.6%, P = 0.0001) and lower OS rate (71.4% vs. 84.2%, P = 0.0000). In multivariate analysis, Rec(+)/Her-2(-) was significantly associated with lower risk of LRR. Rec(-) was an independent prognostic factor for higher risk of DM, decreased DFS and OS. ER, PR and Her-2 are independent prognostic factors for locoregional recurrence and survival in node-positive breast cancer patients treated by mastectomy.

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