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1.
J Surg Oncol ; 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34729779

RESUMO

BACKGROUND AND OBJECTIVES: There are reports of outcomes of elective major cancer surgery during the COVID-19 pandemic. We evaluated if reinforcement of hand hygiene, universal masking, and distancing as a part of pandemic precautions led to a decrease in the incidence of surgical site infections (SSIs) in major oncologic resections. METHODS: Propensity score matching using the nearest neighbor algorithm was performed on 3123 patients over seven covariates (age, comorbidities, surgery duration, prior treatment, disease stage, reconstruction, and surgical wound type) yielding 2614 matched (pre-COVID 1612 and COVID 1002) patients. Conditional logistic regression was used to identify if SSI incidence was lower amongst patients operated during the pandemic. RESULTS: There was a 4.2% (p = 0.006) decrease in SSI in patients operated during the pandemic. On multivariate regression, surgery during the COVID-19 period (odds ratio [OR] = 0.77; 95% confidence interval [CI] = 0.61-0.98; p = 0.03), prior chemoradiation (OR = 2.46; CI = 1.45-4.17; p < 0.001), duration of surgery >4 h (OR = 2.17; 95%CI = 1.55-3.05; p < 0.001) and clean contaminated wounds (OR = 2.50; 95% CI = 1.09-2.18; p = 0.012) were significantly associated with SSI. CONCLUSION: Increased compliance with hand hygiene, near-universal mask usage, and social distancing during the COVID-19 pandemic possibly led to a 23% decreased odds of SSI in major oncologic resections. Extending these low-cost interventions in the post-pandemic era can decrease morbidity associated with SSI in cancer surgery.

2.
Breast ; 60: 177-184, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34655887

RESUMO

BACKGROUND: Young (≤40 years) breast cancers (YBC) are uncommon, inadequately represented in trials and have unique concerns and merit studying. METHODS: The YBC treated with a curative intent between 2015 and 2016 at our institute were analysed. RESULTS: There were 1228 patients with a median age of 36 (12-40) years; 38 (3.1%) had Stage I, 455 (37.1%) - II, 692 (56.3%) -III, and remaining 43 (3.5%) Stage IV (oligo-metastatic) disease; 927 (75.5%) were node positive; 422 (34.4%) were Triple negatives (TNBC), 331 (27%) were HER-2 positive. There were 549 (48.2%) breast conservations and 591 (51.8%) mastectomies of which 62 (10.4%) underwent breast reconstruction. 1143 women received chemotherapy, 617 (53.9%) received as neoadjuvant and 142 (23.1%) had pathological complete response; 934 (81.9%) received adjuvant radiotherapy. At the median follow-up of 48 (0-131) months, 5-year overall and disease-free survival was 79.6% (76.8-82.5) and 59.1% (55.8-62.6). For stage I, II, III and IV, the 5-year overall-survival was 100%, 86.7% (82.8-90.6), 77.3% (73.4-81.2), 69.7% (52.5-86.9) and disease-free survival was 94% (85.9-100), 65.9% (60.3-71.5), 55% (50.5-59.5), and 29.6% (14-45.2) respectively. On multivariate analysis, TNBC and HER-2+ subgroups had poorer survival (p = 0.0035). 25 patients had BRCA mutations with a 5-year DFS of 65.1% (95% CI:43.6-86.6). Fertility preservation was administered in 104 (8.5%) patients; seven women conceived and 5 had live births. Significant postmenopausal symptoms were present in 153 (13%) patients. CONCLUSION: More than half of the YBC in India were diagnosed at an advanced stage with aggressive features leading to suboptimal outcomes. Awareness via national registry and early diagnosis is highly warranted. Menopausal symptoms and fertility issues are prevalent and demand special focus.

3.
Indian J Cancer ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33753616

RESUMO

Background: There is limited access to 1 year of adjuvant trastuzumab in resource-constrained settings. Most randomized studies have failed to prove non-inferiority of shorter durations of adjuvant trastuzumab compared to 1 year However, shorter durations are often used when 1 year is not financially viable. We report the outcomes with 12 weeks of trastuzumab administered as part of curative-intent treatment. Methods: This is a retrospective analysis of patients treated at Tata Memorial Centre, Mumbai, a tertiary care cancer center in India. Patients with human epidermal growth factor receptor (HER2)-positive early or locally advanced breast cancer who received 12 weeks of adjuvant or neoadjuvant trastuzumab with paclitaxel and four cycles of an anthracycline-based regimen in either sequence, through a patient assistance program between January 2011 and December 2012, were analyzed for disease-free survival (DFS), overall survival (OS), and toxicity. Results: A total of 102 patients were analyzed with a data cutoff in September 2019. The median follow-up was 72 months (range 6-90 months), the median age was 46 (24-65) years, 51 (50%) were postmenopausal, 37 (36%) were hormone receptor-positive, and 61 (60%) had stage-III disease. There were 37 DFS events and 26 had OS events. The 5-year DFS was 66% (95% Confidence Interval [CI] 56-75%) and the OS was 76% (95% CI 67-85%), respectively. Cardiac dysfunction developed in 11 (10.7%) patients. Conclusion: The use of neoadjuvant or adjuvant 12-week trastuzumab-paclitaxel in sequence with four anthracycline-based regimens resulted in acceptable long-term outcomes in a group of patients, most of whom had advanced-stage nonmetastatic breast cancer.

4.
Breast ; 56: 88-95, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33640524

RESUMO

BACKGROUND: Pregnancy associated breast cancer (PABC) is a rare entity and defined as breast cancer diagnosed during pregnancy or one-year post-partum. There is sparse data especially from low and middle-income countries (LMIC) and merits exploration. METHODS: The study (2013-2020) evaluated demographics, treatment patterns and outcomes of PABC. RESULTS: There were 104 patients, median age of 31 years; 43 (41%) had triple-negative disease, 31(29.8%) had hormone-receptor (HR) positive and HER2 negative, 14 (13.5%) had HER2-positive and HR negative and 16(15.4%) had triple positive disease. 101(97%) had IDC grade III tumors and 74% had delayed diagnosis. 72% presented with early stage (24, EBC) or locally advanced breast cancer (53, LABC) and received either neoadjuvant (n = 49) or adjuvant (n = 26) chemotherapy and surgery. Trastuzumab, tamoxifen, and radiotherapy were administered post-delivery. At a median follow up of 27 (IQR:19-35) months, the estimated 3-year event-free survival (EFS) for EBC and LABC was 82% (95% CI: 65.2-100) and 56% (95% CI: 42-75.6%) and for metastatic 24% (95% CI: 10.1%-58.5%) respectively. Of the 104 patients, 34 were diagnosed antepartum (AP) and 15 had termination, 2 had preterm and 16 had full-term deliveries(FTDs). Among postpartum cohort (n = 70), 2 had termination, 1 had preterm, 67 had FTDs. 83(including 17 from AP) children from both cohorts were experiencing normal milestones. CONCLUSION: Data from the first Indian PABC registry showed that the majority had delayed diagnosis and aggressive features(TNBC, higher grade). Treatment was feasible in majority and stage matched outcomes were comparable to non-PABCs.


Assuntos
Neoplasias da Mama , Complicações Neoplásicas na Gravidez , Adulto , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Feminino , Idade Gestacional , Humanos , Incidência , Índia/epidemiologia , Mastectomia , Período Pós-Parto , Gravidez , Complicações Neoplásicas na Gravidez/epidemiologia , Complicações Neoplásicas na Gravidez/patologia , Complicações Neoplásicas na Gravidez/terapia , Prognóstico , Receptor ErbB-2 , Sistema de Registros , Análise de Sobrevida
5.
J Plast Reconstr Aesthet Surg ; 74(9): 2176-2183, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33478895

RESUMO

Plastic surgical principles are incorporated with breast conservation surgery (BCS) for cancer to improve aesthetic outcomes. In developing countries, average tumour size is larger at presentation resulting in larger resections often, including overlying skin. LD flap has been the workhorse of partial breast reconstruction. We present an easy and effective alternative to LD flap for carefully selected cases of outer quadrant breast tumours. We report 41 cases of local transposition flap from the lateral chest wall for oncoplastic restoration post BCS, performed between January 2016 and February 2020, at our institution. The median age was 49 years (28-63). Twenty-six patients underwent upfront surgery and 15 after neoadjuvant chemotherapy (NACT). The average pathological tumour size was 2.9 cm (median 2.7 and range 1.1-6) and 1.5 cm (median 1.8 and range 0-3.5) for upfront and post-NACT groups, respectively. The median volume of the resected specimen was 277.8 ml and 253.2 ml for upfront and post-NACT groups, respectively. Three patients (7.5%) had a microscopic positive margin requiring margin revision. Three (7.5%) patients had post-operative minor wound complications and were managed conservatively. At a median follow-up of 14 months (1-36), only 2/19 (10.5%) patients had clinical fat necrosis. Local transposition flap from the lateral chest wall based on dermal and subdermal plexus, carefully designed in selected patients, can be used effectively for the reconstruction of outer quadrant breast defects. It is easy to learn, offers good cosmetic outcome, avoids the morbidity and time of LD flap and saves LD flap for future use.


Assuntos
Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mastectomia Segmentar/métodos , Retalhos Cirúrgicos , Adulto , Estética , Feminino , Sobrevivência de Enxerto , Humanos , Pessoa de Meia-Idade
6.
Clin Breast Cancer ; 21(3): e228-e234, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33046357

RESUMO

INTRODUCTION: Surgery is the primary treatment of phyllodes tumor of the breast, and margins are the most important risk factor associated with local recurrence. We conducted a retrospective audit of 433 patients treated at our center. PATIENTS AND METHODS: Women who presented with phyllodes tumors between 1999 and 2017 were included in the analysis. Data was collected from the hospital medical records, telephonic interviews, and electronic mail. RESULTS: Of the 433 women included in this study, 177 (40.9%) had benign phyllodes tumors, 84 (19.4%) were borderline, 131 (30.3%) were malignant, and 41 (9.5%) had sarcoma. A history of previous excision was noted in 154 (35.6%) patients, of which 104 presented with local recurrence. Of the total patients, 209 (48.3%) underwent breast conservation surgery; the median pT was 6 cm. At a median follow-up of 37.9 months, the 5-year disease-free survival (DFS) was 82.9%. On multivariate analysis, the factors that impacted DFS were histology (hazard ratio, 4.1; 95% confidence interval [CI], 1.5-10.9; P = .005) and history of previous excision biopsy (hazard ratio, 3.39; 95% CI, 1.76-6.52; P < .001). We analyzed 231 women who presented without any prior excision separately, wherein at a median follow-up of 44.1 months, the DFS was 92.1% (95% CI, 92.05%-92.15%). In addition, less recurrences were noted in this cohort (5.6% [13/231] in no-excision biopsy vs. 12.5% with surgery done prior to presentation to our institute). CONCLUSION: A previous history of excision and the histologic subtype of phyllodes tumor are factors that have an impact on DFS, thus emphasizing the need for appropriate surgical planning and en bloc excision of the phyllodes at presentation.

7.
Ecancermedicalscience ; 14: 1092, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014134

RESUMO

Triple negative breast carcinoma is a problematic subtype with poor outcomes. Many clinical trials are underway to find possible target to increase treatment options. Epidermal growth factor receptor (EGFR) has emerged as one such molecule which is over expressed in some of these patients and can be targeted by tyrosine kinase inhibitors. We describe a diagnostically challenging case of metastatic breast carcinoma, with extensive lung disease and poor Eastern Cooperative Oncology Group (ECOG) performance status, which expressed an uncommon EGFR mutation (Exon 21L861Q) and which benefitted from erlotinib following failure of all primary treatment modalities. The case uncovers the presence of these unusual mutations in breast carcinoma and highlights the importance of performing molecular analysis and the appropriate targeted therapy. This approach can be an important problem-solving tool, especially in cases where the patient is not fit for the other standard treatment options.

9.
JCO Glob Oncol ; 6: 1184-1191, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32735491

RESUMO

PURPOSE: The role of axillary conservation after neoadjuvant chemotherapy (NACT) is debatable. We routinely carry out complete axillary lymph node dissection (ALND). This study was conducted to understand the pathologic axillary complete response (pAxCR) after NACT. MATERIALS AND METHODS: We evaluated a prospective database of patients with breast cancer who underwent surgery after NACT in the year 2017 at our institution. NACT was administered to downstage locally advanced breast cancer or facilitate breast-conservation surgery. RESULTS: Of 793 patients who underwent surgery after NACT, 97(12.2%) had cN0 disease, 407 (51.3%) had cN1, 262 (32%) had cN2, and 27 (3.4%) had cN3 at presentation. Eighty-eight patients (11.1%) had cT1-2 primary tumor stage, and 623 patients (78.6%) had cT3-4 primary tumor stage; primary tumor stage details were unavailable for 82 patients (10.3%). The median age was 46 years (range, 21-74 years). On histopathology, the overall pAxCR rate was 52.8%. In the cN1 and cN2 settings, 58.7% and 36.6% of patients achieved ypN0 status, respectively. The overall pathologic complete response rate was 22.64% (161 of 711 patients). On univariable analysis, cN stage, histologic grade, hormone receptor status, NACT duration, and lymphovascular invasion were significantly associated with pAxCR (P <.001). On logistic regression, prechemotherapy cN status (odds ratio [OR], 3.08; 95% CI, 2.18 to 4.37; P <.001), estrogen and progesterone receptor status (OR, 0.34; 95% CI, 0.3 to 0.4; P <.001), and administration of both chemotherapy regimens preoperatively (OR, 0.66; 95% CI, 0.45 to 0.97; P <.05) predicted pAxCR. CONCLUSION: At least half of patients with cN1 and a third of patients with cN2 breast cancer who develop pAxCR may be suitable candidates for axillary conservation. A careful postchemotherapy assessment followed by a conservative axillary procedure may be an alternative to ALND, but this needs to be studied prospectively.


Assuntos
Excisão de Linfonodo , Terapia Neoadjuvante , Axila , Humanos , Mastectomia , Pessoa de Meia-Idade , Esterilização
11.
SLAS Technol ; 24(3): 354-356, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30816065

RESUMO

The demand for automation in the analytical laboratory is high. In contrast to well-automated bioscreening and high-throughput and high-content screening processes, analytical measurement procedures are complex in their structure and changing frequently. Not only do robotic units have to perform transportation or specific single tasks, but also flexible robots are needed to cover several tasks, including transportation and direct sample manipulation. Due to their human-like structure, dual-arm robots are predestined for analytical measurement processes. A new study published in the journal Energies presents a novel integration of electronic piston pipettes into an automation system using a dual-arm robot to perform liquid handling tasks similar to human operators. In this commentary, the main findings are highlighted and discussed.


Assuntos
Automação Laboratorial/métodos , Técnicas de Química Analítica/métodos , Robótica/métodos , Manejo de Espécimes/métodos
12.
J Glob Oncol ; 5: 1-8, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30811304

RESUMO

PURPOSE: A complete axillary lymph node (ALN) dissection is therapeutic in node-positive breast cancer. Presently, there is no international consensus regarding anatomic levels to be addressed in complete axillary dissection. We assessed the burden of disease in level III axilla. MATERIALS AND METHODS: A prospectively maintained database was assessed for 1,591 consecutive patients with nonmetastatic breast cancer registered at Tata Memorial Center, Mumbai, between January 2009 and December 2014. RESULTS: A median of four (zero to 20) level III ALNs were dissected and a median of two (one to 17) nodes were positive. A total of 27.3% (434 of 1,591) patients had level III ALN metastasis, and 4.7% of patients had positive interpectoral nodes. Some 53.2% of patients had level III metastases in the presence of four or more positive level I and II ALNs. A total of 9.4% of patients had level III involvement when one to three ALNs were positive in level I and II ( P < .001). Some 53.2% of patients had level III metastases in the presence of four or more positive level I and II ALNs. On logistic regression analysis, four or more positive ALNs in level I or II ( P < .001), inner/central quadrant tumor location ( P = .013), and perinodal extension ( P < .001) were associated with level III ALN involvement. At a median follow-up of 36 months, the disease-free survival was significantly worse for level III ALN metastases on univariate analysis ( P < .001). On multivariate Cox regression analysis, histologic grade ( P = .006), four or more positive ALNs ( P < .001), hormone receptor status ( P < .001), and tumor size ( P = .037) were independent prognostic factors for disease-free survival. CONCLUSION: The axillary nodal burden is high in patients with breast cancer in developing countries like India. One of two women with four or more positive level I and II ALNs may have residual disease in level III if it is not cleared during surgery. Intraoperative interpectoral space clearance should be considered in the presence of either palpable interpectoral lymph nodes or multiple positive ALNs.


Assuntos
Neoplasias da Mama/cirurgia , Excisão de Linfonodo/métodos , Linfonodos/patologia , Metástase Linfática/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Índia , Modelos Logísticos , Linfonodos/cirurgia , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Carga Tumoral , Adulto Jovem
13.
Indian J Cancer ; 55(1): 16-22, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30147088

RESUMO

Background: Survival studies may serve as benchmarks to develop cancer-related policies and estimate baseline survival rates in a given patient population. Materials and Methods: We carried out a retrospective audit of cases managed in 2009 and now report the disease-free survival (DFS) in early breast cancer (EBC) and locally advanced breast cancer (LABC) in patients registered at a tertiary cancer center in India. Results: The study included 2192 patients with breast cancer with ages ranging from 18 years to 94 years with a median of 50 years. Of these, 888 (40.5%) were EBCs Stage I and II, 833 (38%) were LABCs (Stage III), and 471 (21.5%) were de novo metastatic or relapsed cancers at presentation. The 5-year DFS in the women with EBC was 85.5% and in LABC, it was 67.7%, P < 0.001. The factors adversely affecting DFS in EBC were node metastasis (P < 0.001), higher metastatic nodes (P < 0.001), hormone receptor negativity (P = 0.001), and human epidermal growth factor receptor 2 (Her2neu) positivity (P = 0.033). In the multivariate Cox regression analysis in EBC, node-positive status (hazard ratio [HR] 2.28, 95% confidence interval [CI] 1.51-3.45, P < 0.001) and hormone receptor negative tumors (HR 1.96, 95% CI 1.30-2.94, P = 0.001) significantly affected DFS in EBC. The factors adversely affecting DFS in LABC in the univariate analysis were node metastasis (P < 0.001), increasing numbers of nodes (P < 0.001), presence of lymphovascular emboli (LVE) (P < 0.01), mastectomy (P < 0.001), and Her2neu positivity (P = 0.03). In the multivariate Cox regression analysis, node positivity (HR 2.96, 95% CI 2.04-4.29, P < 0.0001), presence of LVE (HR 1.47, 95% CI 1.06-2.04, P = 0.023), and mastectomy (HR 1.49, 95% CI 1.06-2.10, P = 0.023) adversely impacted DFS in LABC. Conclusions: The survival rates in this study are equal to the documented global rates; nodal disease burden emerged as the most important prognostic factor. In addition, in EBCs, a lack of hormone receptor expression and in LABC, Her2neu overexpression appear to worsen the outcome.


Assuntos
Neoplasias da Mama/epidemiologia , Recidiva Local de Neoplasia/epidemiologia , Receptor ErbB-2/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Mastectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Centros de Atenção Terciária , Resultado do Tratamento , Adulto Jovem
15.
BMC Cancer ; 15: 546, 2015 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-26205655

RESUMO

BACKGROUND: Immunohistochemical assessment of proliferation may provide additional prognostic information in early breast cancer. However, due to a lack of methodological standards proliferation markers are still not routinely used for determining therapy. Even for Ki67, one of the most widely-studied markers, disagreements over the optimal cutoff exist. Improvements in digital microscopy may provide new avenues to standardise and make data more reproducible. METHODS: We studied the immunohistochemical expression of three markers of proliferation: Ki67, Mini-Chromosome Maintenance protein 2 and Geminin, by conventional light microscope and digital imaging on triplicate TMAs from 309 consecutive cases of primary breast cancers. Differences between the average and the maximum percentage reactivity in tumour cell nuclei from the three TMA cores were investigated to assess the validity of the approach. Time-dependent Receiver Operating Characteristic curves were utilized to obtain optimal expression level cut-offs, which were then correlated with clinico-pathological features and survival. RESULTS: High concordance between conventional and digital scores was observed for all 3 markers (Ki67: rs = 0.87, P < 0.001; MCM2: rs = 0.94, P < 0.001; and Geminin: rs = 0.86, P < 0.001; Spearman's rank). There was no significant difference according to the number of TMA cores included for either Ki67 or MCM2; analysis of two or three cores produced comparable results. Higher levels of all three proliferation markers were significantly associated with higher grade (P < 0.001) and ER-negativity (P < 0.001). Optimal prognostic cut-offs for percentage expression in the tumour were 8 %, 12 and 2.33 % for Ki67, MCM2 and Geminin respectively. All 3 proliferation marker cutoffs were predictive of 15-year breast cancer-specific survival in univariable Cox regression analyses. In multivariable analysis only lymph node status (HR = 3.9, 95 % CI = 1.79-8.5, P = 0.0006) and histological grade (HR = 1.84, 95 % CI = 1-3.38, P = 0.05) remained significantly prognostic. CONCLUSIONS: Here we show that. MCM2 is a more sensitive marker of proliferation than Ki67 and should be examined in future studies, especially in the lymph node-negative, hormone receptor-positive subgroup. Further, digital microscopy can be used effectively as a high-throughput method to evaluate immunohistochemical expression.


Assuntos
Neoplasias da Mama/patologia , Diagnóstico por Imagem/métodos , Detecção Precoce de Câncer/métodos , Geminina/metabolismo , Antígeno Ki-67/metabolismo , Componente 2 do Complexo de Manutenção de Minicromossomo/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Análise Serial de Tecidos
16.
Cancer Discov ; 5(5): 488-505, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25770156

RESUMO

UNLABELLED: Triple-negative breast cancers (TNBC) are characterized by a wide spectrum of genomic alterations, some of which might be caused by defects in DNA repair processes such as homologous recombination (HR). Despite this understanding, associating particular patterns of genomic instability with response to therapy has been challenging. Here, we show that allelic-imbalanced copy-number aberrations (AiCNA) are more prevalent in TNBCs that respond to platinum-based chemotherapy, thus providing a candidate predictive biomarker for this disease. Furthermore, we show that a high level of AiCNA is linked with elevated expression of a meiosis-associated gene, HORMAD1. Elevated HORMAD1 expression suppresses RAD51-dependent HR and drives the use of alternative forms of DNA repair, the generation of AiCNAs, as well as sensitizing cancer cells to HR-targeting therapies. Our data therefore provide a mechanistic association between HORMAD1 expression, a specific pattern of genomic instability, and an association with response to platinum-based chemotherapy in TNBC. SIGNIFICANCE: Previous studies have shown correlation between mutational "scars" and sensitivity to platinums extending beyond associations with BRCA1/2 mutation, but do not elucidate the mechanism. Here, a novel allele-specific copy-number characterization of genome instability identifies and functionally validates the inappropriate expression of the meiotic gene HORMAD1 as a driver of HR deficiency in TNBC, acting to induce allelic imbalance and moderate platinum and PARP inhibitor sensitivity with implications for the use of such "scars" and expression of meiotic genes as predictive biomarkers.


Assuntos
Proteínas de Ciclo Celular/genética , Expressão Gênica , Genômica , Recombinação Homóloga , Neoplasias de Mama Triplo Negativas/genética , Desequilíbrio Alélico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Núcleo Celular/genética , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Instabilidade Cromossômica , Análise por Conglomerados , Variações do Número de Cópias de DNA , Resistencia a Medicamentos Antineoplásicos/genética , Perfilação da Expressão Gênica , Inativação Gênica , Humanos , Platina/administração & dosagem , Polimorfismo de Nucleotídeo Único , RNA Interferente Pequeno/genética , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia
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