BRCAness and prognosis of triple-negative breast cancer patients treated with neoadjuvant chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12111-e12111 ◽  
Author(s):  
Sadako Akashi-Tanaka ◽  
Yuichi Tanino ◽  
Yutaka Yamamoto ◽  
Hiroshi Nishimiya ◽  
Mutsuko Yamamoto-ibusuki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Needle Biopsy ◽  
Triple Negative ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Core Needle ◽  
Brca 1 ◽  
Dna Repair Inhibitors ◽  
Dependent Probe

e12111 Background: Triple-negative breast cancers (TNBCs) consist of patients which are recalcitrant to chemotherapy. Dysfunction of BRCA, called “BRCAness” may be predictive of sensitivity to DNA repair inhibitors. However, adequate assay of “BRCAness” are still not confirmed. Multiplex ligation-dependent probe amplification (MLPA) with the Probemix P376-B2 BRCA1ness (MRC-Holland, The Netherlands) can be one method to determine BRCAness. We previously reported that “BRCAness” by MLPA predict resistance to taxane during neoadjuvant chemotherapy (NAC) and poor outcome. In the present study, we evaluated the clinical significance of BRCAness in a multicenter retrospective study. Methods: The data on 94 patients with TNBC treated with NAC were obtained from 3 hospitals in Japan. Most of them were treated by anthracyclines plus taxanes in 86 patients between 2005 and 2015. BRCAness was determined by core needle biopsy (CNB) specimens prior to NAC and surgical specimens. Genes from those specimens were amplified by MLPA, and the amplicons were scored. BRCA1-like type (BRCAness) was determined by tumors with greater than 0.5 Results: pCR (ypT0/Tis/N0) rate was 46%. Recurrence occurred in 22 patients, 11 of whom died from breast cancer. (1) BRCA1-like type accounted for 51 patients while the sporadic type in 43 patients in CNB specimens. No major differences in pCR rates and recurrence were observed between the BRCA1-like type and sporadic type (19/51 vs. 24/43), respectively. Patients with BRCA1-like tended to resist taxane than those with sporadic type when treated with taxane first. Among the 51 non-pCR patients, 19 were BRCA1-like type and 31 were sporadic type upon surgical specimens. Patients with a BRCA1-like tumors had more recurrences, than non-BRCA-1-like (13/19 vs. 9/31, respectively, P < 0.01). Conclusions: Tumors with BRCA-1 like tended to resist taxane than sporadic type when treated by taxane first. Anthracycline first might mask the progression during taxane regimen. Patients with BRCA1-like after NAC had more recurrences than those with sporadic type. Further study is needed to evaluate the significance of BRCAness.

The discordance of the ER, PR, and HER2 status after neoadjuvant chemotherapy in breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12037-e12037
Author(s):  
Basak Oven Ustaalioglu ◽  
Ahmet Bilici ◽  
Fugen Vardar Aker ◽  
Burcak Erkol ◽  
Mehmet Aliustaoglu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Core Needle Biopsy ◽  
Needle Biopsy ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Her2 Status ◽  
Breast Cancer Patients ◽  
Core Needle

e12037 Background: Neoadjuvant chemotherapy(NAC) is the accepted approach for women with locally advanced breast cancer with technically inoperable disease. Systemic treatment is mainly based on the presence of the Estrogen (ER) receptor, Progesterone (PR) receptor and HER2 status on the core needle biopsy prior to treatment. Previously, discordance of the hormone receptor (HR) status was reported as 8-33% in the breast cancer patients after NAC. In here, we evaluated the HR and HER2 discordance after NAC in locally advanced breast cancer patients. Methods: We reviewed the data of 849 breast cancer patients retrospectively. The pathological specimens of core needle biopsy and operation specimens were re-evaluated for HR and HER2 status in 38 patients who had been treated with NAC. The changing of HR and HER2 status after chemotherapy was defined as discordance. The relationship between clinicopathological parameters and discordance and significance of them for disease-free survival (DFS) was analyzed by chi-square and univariaty test. Results: Over 80% of patients were clinically stage III breast cancer. Out of 24 patients were premenapouse and median age was 44.5(30-94). The patients were received median 4(1-6) cycles of NAC as 2 of them were only hormonotherapy, 8 were only antracycline and others were both antracycline and taxanes. Nearly 80% of patients were performed modified radical mastectomy(MRM).Postoperatively median tumor size was 1.6cm(0-10) and median dissected lymph nodes was 14(0-28). After operation, 4(10.5%), 8(21.1%) and 8(21.1%) discordance were detected for ER, PR and HER2 respectively. While HER2 discordance were related with recurrence(p=0.01) and PR discordance(p=0.04), ER discordance was related with only patological stage(p=0.03). At the median follow-up of 15.7 months, 5 year DFS rate and time were 30% and 30.4 months(18.7-42.2), respectively. Operation type, stage, lymphovascular invasion, perineural invasion were found to be significant for DFS, HR and HER2 discordance was not related with DFS. Conclusions: Until more definitive results will be obtained from future studies, receptor status of the residual tumor after NAC should be retested.

Is There a Bias Against Obese Patients in the Treatment of Breast Cancer?

2020 ◽  
pp. 000313482098487
Author(s):  
Melinda Wang ◽  
Julian Huang ◽  
Anees B. Chagpar
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Prophylactic Mastectomy ◽  
Implicit Bias ◽  
Treatment Decision ◽  
Obese Patients ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Immediate Reconstruction

Background Patient and tumor characteristics often coincide with obesity, potentially affecting treatment decision-making in obese breast cancer patients. Independent of all of these factors, however, it is unclear whether obesity itself impacts the decision to offer patients undergoing mastectomy breast reconstruction, postmastectomy radiation therapy (PMRT), or neoadjuvant chemotherapy. We sought to determine whether implicit bias against obese breast cancer patients undergoing mastectomy plays a role in their treatment. Methods Medical records of breast cancer patients undergoing mastectomy from January 2010 to April 2018 from a single institution were retrospectively reviewed, separated into obese (BMI ≥30) and nonobese (BMI <30) categories, and compared using nonparametric statistical analyses. Results Of 972 patients, 291 (31.2%) were obese. Obese patients were more likely to have node-positive, triple-negative breast cancers ( P = .026) and were also more likely to have other comorbidities such as a history of smoking ( P = .026), hypertension ( P < .001), and diabetes ( P < .001). Receipt of immediate reconstruction and contralateral prophylactic mastectomy did not vary between obese and nonobese patients. While obese patients were more likely to undergo neoadjuvant chemotherapy (26.5% vs. 18.1%, P = .004) and PMRT (33.0% vs. 23.4%, P = .003), this did not remain significant when controlling for comorbidities and clinicopathologic confounders. Conclusion Obese patients present with more aggressive tumors and often have concomitant comorbidities. Independent of these factors, however, differences in the treatment of patients undergoing mastectomy do not seem to be affected by an implicit bias against obese patients.

scholarly journals Regression of Triple-Negative Breast Cancer in a Patient-Derived Xenograft Mouse Model by Monoclonal Antibodies against IL-12 p40 Monomer

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 259
Author(s):  
Madhuchhanda Kundu ◽  
Sumita Raha ◽  
Avik Roy ◽  
Kalipada Pahan
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Transforming Growth Factor ◽  
Healthy Controls ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Patient Derived Xenograft

Although some therapies are available for regular breast cancers, there are very few options for triple-negative breast cancer (TNBC). Here, we demonstrated that serum level of IL-12p40 monomer (p40) was much higher in breast cancer patients than healthy controls. On the other hand, levels of IL-12, IL-23 and p40 homodimer (p402) were lower in serum of breast cancer patients as compared to healthy controls. Similarly, human TNBC cells produced greater level of p40 than p402. The level of p40 was also larger than p402 in serum of a patient-derived xenograft (PDX) mouse model. Accordingly, neutralization of p40 by p40 mAb induced death of human TNBC cells and tumor shrinkage in PDX mice. While investigating the mechanism, we found that neutralization of p40 led to upregulation of human CD4+IFNγ+ and CD8+IFNγ+ T cell populations, thereby increasing the level of human IFNγ and decreasing the level of human IL-10 in PDX mice. Finally, we demonstrated the infiltration of human cytotoxic T cells, switching of tumor-associated macrophage M2 (TAM2) to TAM1 and suppression of transforming growth factor β (TGFβ) in tumor tissues of p40 mAb-treated PDX mice. Our studies identify a possible new immunotherapy for TNBC in which p40 mAb inhibits tumor growth in PDX mice.

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