Neoadjuvant Chemotherapy In Women Research Articles

Abstract PO4-03-09: Profile of circulating natural killer cells in stage III triple negative breast cancer before and after neoadjuvant chemotherapy

Abstract Background: Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. The treatment for locally advanced disease is based on neoadjuvant chemotherapy and immunotherapy, with complete pathological response (pCR) serving as a predictor of disease-free survival. Although the presence of immune cell infiltration in the tumor has a favorable prognostic impact, there is a lack of predictive biomarkers for complete pathological response to neoadjuvant chemotherapy (NAC). Objective: to analyze the profile of circulating Natural Killer (NK) cells and NK subpopulations (NK FAS+ and NK PD1+) in association with the occurrence of complete pathological response after neoadjuvant chemotherapy in women with clinical stage III TNBC. Methods: This was a longitudinal prospective and translational cohort study, including women aged 18 to 60 years with stage III TNBC diagnosed between March 2015 and July 2017, with a follow-up of 24 months. A comparison control group consisted of 30 healthy women aged 18 to 60 years without prior or current cancer diagnosis and no family history of breast cancer. Peripheral blood samples were collected before NAC and before surgery. Flow cytometry was used to analyze the percentage levels of NK cells and NK subpopulations (NK FAS+ and NK PD1+). The Shapiro-Wilk test was initially applied to assess the normality of quantitative variables. The non-parametric Mann-Whitney test was used for comparison between two groups. The statistical significance level was set at p< 0.05. Overall survival (OS) was estimated using the Kaplan-Meier method. Statistical analysis was performed using GraphPad Prism v9.5.1. Results: The median age was 45 years. Stage IIIA was identified in 28% of the patients, while IIIB was observed in 72%. Regarding pathological response, 14 patients (48%) achieved pCR, while 15 patients (52%) had a non-complete pathological response (non-pCR). The 2-year OS was 86%, with no median reached. Higher percentage levels of NK cells, NK FAS+, and NK PD1+ were observed in the patient group compared to the control group, with significant differences. There was a significant increase in the percentage levels of NK cells after NAC compared to pre-NAC levels, and a reduction in NK PD1+ levels. NK cell levels were significantly higher in patients with stage IIIA compared to stage IIIB, while NK FAS+ levels were lower. NK cell and NK FAS+ subpopulation levels were significantly higher in patients who achieved pCR compared to non-pCR patients, with no difference in NK PD1+ cell levels. Conclusions: Elevated levels of circulating NK cells and NK FAS+ subpopulation collected from peripheral blood before NAC may serve as potential biomarkers for pCR in patients with TNBC. Citation Format: Luiz Jose de Barros Batista, Jurema Telles, Candice Santos, Ariani Souza, Marcelo Salgado, Leuridan Torres. Profile of circulating natural killer cells in stage III triple negative breast cancer before and after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-03-09.

Inflammatory indicators as a prognostic factor of clinical response in locally advanced breast cancer (LABC) patients receiving neoadjuvant chemotherapy (NAC)

ObjectivesBreast cancer is a prevalent and fatal cancer worldwide. Neoadjuvant chemotherapy is a treatment option used to reduce tumor size in patients with locally advanced breast cancer. The neutrophil–lymphocyte ratio (NLR), lymphocyte–monocyte ratio (LMR), and platelet–lymphocyte ratio (PLR) are inflammatory markers that have been studied as prognostic factors in breast cancer. This cross-sectional study aimed to investigate the role of NLR, LMR, and PLR in the clinical response to neoadjuvant chemotherapy in women with locally advanced breast cancer. Materials and methodsWe used a cross-sectional research design for this study with the aim of observing the relation between NLR, LMR, and PLR and the clinical response of neoadjuvant chemotherapy. The study was conducted in Cipto Mangunkusumo General Hospital. We analyzed the medical records of 84 patients treated with neoadjuvant chemotherapy between 2016 and 2021. ResultsOur study found that majority of the subjects receives CAF combination of NAC with inoperable breast cancer. Most of the subjects have luminal B type of breast cancer and no clinical response to chemotherapy regimen. Surgery has significant association with clinical response in patients receiving NAC (P = <.001). There are no significant correlation between NLR, LMR, and PLR with clinical response to neoadjuvant chemotherapy. However, we did observe a significant association between NLR and 1-year mortality rate. ConclusionIn conclusion, significant association between NLR and 1-year morality rate suggest that NLR may serve as a useful prognostic factor in breast cancer patients receiving neoadjuvant chemotherapy.

Systematic Review of the Survival Outcomes of Neoadjuvant Chemotherapy in Women with Malignant Ovarian Germ Cell Tumors.

Randomized clinical trials assessing the efficacy of neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer have predominantly included women with high-grade serous carcinomas. The response rate and oncological outcomes of NACT for malignant ovarian germ cell tumors (MOGCT) are poorly understood. This study aimed to examine the effects of NACT on women with MOGCT by conducting a systematic review of four public search engines. Fifteen studies were identified, and a further descriptive analysis was performed for 10 original articles. In those studies, most women were treated with a bleomycin, etoposide, and cisplatin regimen, and one to three cycles were used in most studies. Four studies comparing NACT and primary debulking surgery showed similar complete response rates (n = 2; pooled odds ratio [OR] 0.90, 95% confidence interval [CI] 0.15-5.27), comparable overall survival (n = 3; 87.0-100% versus 70.0-100%), disease-free survival (n = 3; 87.0-100% versus 70.0-100%), recurrence rate (n = 1; OR 3.50, 95%CI 0.38-32.50), and adverse events rate from chemotherapy between the groups. In conclusion, NACT may be considered for the management of MOGCT; however, possible candidates for NACT use and an ideal number of NACT cycles remain unknown. Further studies are warranted to validate the efficacy of NACT in advanced MOGCT patients.

Temporal Trends and Factors Associated with Receipt of Post-mastectomy Radiation After Neoadjuvant Chemotherapy in Women with cT3 Breast Cancer.

Given the potential impact of increasingly effective neoadjuvant chemotherapy (NACT) on post-mastectomy radiotherapy (PMRT) recommendations, we examined temporal trends in post-NACT PMRT for cT3 breast cancer. We identified women ≥ 18 years in the National Cancer Database (NCDB) diagnosed 2004-2019 with cT3N0-1M0 breast cancer treated with chemotherapy and mastectomy. Multivariable logistic regression and Cox proportional hazards models were used to estimate associations between pathologic NACT response [complete response (CR), partial response (PR), or no response (NR); or disease progression (DP)] and PMRT and between PMRT and overall survival (OS), respectively. We identified 39,901 women (Asian/Pacific Islander 1731, Black 5875, Hispanic 3265, White 27,303). Among cN0 patients with CR, PMRT rates declined from 67% in 2004 to 35% in 2019 but remained unchanged for patients with DP. Relative to NR, CR [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.29-0.46] and PR (OR 0.44, 95% CI 0.36-0.55) in cN0 patients were associated with lower odds of PMRT while DP (OR 1.33, 95% CI 1.05-1.69) was associated with higher odds. Among cN1 patients, PMRT rates decreased from 90% to 73% for CR between 2005 and 2019 and increased from 76% to 82% for DP between 2004 and 2019. Relative to NR, CR (OR 0.78, 95% CI 0.63-0.95) was associated with lower odds of PMRT while DP (OR 1.93, 95% CI 1.58-2.37) was associated with higher odds. PMRT was associated with improved OS among cN1 patients (hazard ratio (HR) 0.77, 95% CI 0.67-0.88). CR was associated with decreased PMRT receipt over time, while temporal trends following PR and DP differed by cN status, suggesting that nodal involvement guided PMRT receipt more than in-breast disease.

ASO Visual Abstract: Temporal Trends and Factors Associated with Receipt of Post-mastectomy Radiation After Neoadjuvant Chemotherapy in Women with cT3 Breast Cancer.

ASO Visual Abstract: Temporal Trends and Factors Associated with Receipt of Post-mastectomy Radiation After Neoadjuvant Chemotherapy in Women with cT3 Breast Cancer.

Oncologic safety of breast conservation following NACT in women with locally advanced breast cancer.

Breast conservation surgery (BCS) is the accepted standard of treatment for early breast cancer, with evidence from randomized controlled and population-based studies. The oncological outcome of BCS in locally advanced breast cancer (LABC) is mainly available from retrospective series with a small sample size and a shorter follow-up duration. A retrospective observational study of 411 non-metastatic LABC patients who received neoadjuvant chemotherapy (NACT) followed by surgery from 2011 to 2016. We retrieved the data from a prospectively maintained database and electronic medical records. Survival data were analyzed by Kaplan-Meier curves and Cox regression using Statistical Package for the Social Sciences 25 and STATA 14. 146/411 (35.5%) women had BCS with a margin positivity rate of 3.42%. With a median follow-up of 64 months (IQR 61, 66), the local relapse rate was 8.9% in BCS and 8.3% after mastectomy. The estimated 5-year locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), distant disease-free survival (DDFS) and overall survival (OS) rates of BCS were 86.9%, 63.9%, 71% and 79.3%, and 90.1%, 57.9%, 58.3% and 71.5% in the mastectomy group. On univariate analysis, BCS showed superior survival outcomes compared to mastectomy (unadjusted HR (95% CI) for RFS: 0.70 (0.50-1), DDFS: 0.57 (0.39-0.84), OS: 0.58 (0.36-0.93)). After adjusting for age, cT stage, cN stage, poorer chemotherapy response (ypT0/is, N0) and radiotherapy, BCS and mastectomy groups were found comparable in terms of LRFS (HR: 1.1, 0.53-2.3), DDFS (HR: 0.67, 0.45-1.01), RFS (HR: 0.80, 0.55-1.17) and OS (HR: 0.69, 0.41-1.14). BCS is technically feasible in LABC patients. LABC patients who respond well to NACT can be offered BCS without compromising survival outcomes.

Abstract P4-06-05: Response to neoadjuvant chemotherapy among women with triple-negative breast cancer by HER2 expression status

Abstract Background: - Low levels of HER2 expression among women with HER2-negative breast cancer is an emerging target. In addition, prior studies have suggested that low levels of HER2 expression might confer resistance to chemotherapy among women with triple-negative breast cancer (TNBC). In this study, we assess the response to neoadjuvant chemotherapy among women with TNBC with varying degrees of HER2 expression. Methodology: - Utilizing the National Cancer Database, we identified adult women treated with neoadjuvant chemotherapy for a diagnosis of clinical TNM stage I to III triple-negative invasive ductal carcinoma of the breast between the years 2010 and 2018. Baseline characteristics were compared between HER2 immunohistochemistry (IHC) scores of 0, 1 +, and 2+ (Women with HER2 2+ expression had to be negative for amplification in the HER2 gene by FISH) using Chi-square for categorical variables. The odds of achieving a complete pathological response were compared among women with different HER2 expression statuses in a multivariate logistic regression model adjusting for age, race, ethnicity, grade of the tumor, and clinical TNM stage at diagnosis. A multivariate cox proportional hazards regression model was used to identify the prognostic effect of HER2 expression on overall survival (OS) adjusting for age at diagnosis, race, ethnicity, grade of tumor, and clinical TNM stage at diagnosis. Results: - A total of 11,038 women with HER2 IHC score of 0, 8,718 women with a score of 1+ and 2,700 women with a score of 2+ were included in the final analysis. The median age at diagnosis was 52 for women with a HER2 IHC score of 0, 53 for women with a HER2 IHC score of 1+ and 54 for women with an IHC score of 2+/FISH negative. The rates of complete pathological response among women with HER2 IHC scores of 0, 1+, and 2+ were 39.5%, 38.1%, and 36.1% respectively. In multivariate analysis, a significant difference in the odds of achieving complete pathological response was not observed for women with HER2 1+ (OR: 1.1, 95% CI: 0.95-1.20, p = 0.3) or HER2 2+ (OR: 0.9, 95% CI: 0.7-1.0, p = 0.1) tumors compared to women with HER2 IHC score of 0. In multivariate Cox regression analysis, women with TNBC with HER2 IHC score 2+ were found to have a better OS (Hazard Ratio [HR]: 0.88, 95% CI: 0.80-0.97, p = 0.01) compared to women with HER2 IHC score of 0 whereas a significant difference in OS was not observed between women with HER2 IHC scores of 0 and 1+ (HR: 0.95, 95% CI: 0.89–1.01, p = 0.1). Conclusion: - This study demonstrates that HER2 expression status does not influence the rates of complete pathological response to neoadjuvant chemotherapy in women with TNBC. However, women with HER2 IHC score of 2+ were found to have a favorable prognosis, which needs to be evaluated further in future studies. Citation Format: Pravash Budhathoki, Anish Shah, Suman Gaire, Utsav Joshi, Siddhartha Yadav. Response to neoadjuvant chemotherapy among women with triple-negative breast cancer by HER2 expression status [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-06-05.

Development and Assessment of a Novel Core Biopsy-Based Prediction Model for Pathological Complete Response to Neoadjuvant Chemotherapy in Women with Breast Cancer.

Purpose: Pathological complete response (pCR), the goal of NAC, is considered a surrogate for favorable outcomes in breast cancer (BC) patients administrated neoadjuvant chemotherapy (NAC). This study aimed to develop and assess a novel nomogram model for predicting the probability of pCR based on the core biopsy. Methods: This was a retrospective study involving 920 BC patients administered NAC between January 2012 and December 2018. The patients were divided into a primary cohort (769 patients from January 2012 to December 2017) and a validation cohort (151 patients from January 2017 to December 2018). After converting continuous variables to categorical variables, variables entering the model were sequentially identified via univariate analysis, a multicollinearity test, and binary logistic regression analysis, and then, a nomogram model was developed. The performance of the model was assessed concerning its discrimination, accuracy, and clinical utility. Results: The optimal predictive threshold for estrogen receptor (ER), Ki67, and p53 were 22.5%, 32.5%, and 37.5%, respectively (all p < 0.001). Five variables were selected to develop the model: clinical T staging (cT), clinical nodal (cN) status, ER status, Ki67 status, and p53 status (all p ≤ 0.001). The nomogram showed good discrimination with the area under the curve (AUC) of 0.804 and 0.774 for the primary and validation cohorts, respectively, and good calibration. Decision curve analysis (DCA) showed that the model had practical clinical value. Conclusions: This study constructed a novel nomogram model based on cT, cN, ER status, Ki67 status, and p53 status, which could be applied to personalize the prediction of pCR in BC patients treated with NAC.

Adoption of minimally invasive surgery after neoadjuvant chemotherapy in women with metastatic uterine cancer (462)

Objectives: The utilization of neoadjuvant chemotherapy (NACT) for advanced-stage uterine cancer is increasing. However, the relationship between NACT administration and the type of surgical approach used for interval debulking surgery (IDS) remains unknown. We analyzed the use and outcomes of open versus minimally invasive surgery (MIS) for women with stage IV uterine cancer who received NACT and underwent IDS. Methods: The National Cancer Database was used to identify women with stage IV uterine cancer diagnosed from 2010 to 2017 and treated with NACT. Among women who underwent IDS, overall survival (OS) was compared between those who underwent laparotomy versus a minimally invasive approach. To account for imbalances in confound- ers, a propensity score analysis using inverse probability of treatment weighting (IPTW) was performed. Cox proportional hazards models to compare all-cause mortality between the groups were examined. Results: A total of 1,618 women with stage IV uterine cancer who received NACT were identified. Overall, minimally invasive IDS was performed in 31.1% of the cohort. MIS use increased from 16.2% in 2010 to 40.4% in 2017 (p<0.001). More recent years of diagnosis and performance of surgery at a comprehensive cancer center or integrated network cancer center were associated with increased use of MIS (p<0.05). Women with serous and clear cell tumors and carcinosarcomas (compared to endometrioid tumors), as well as Medicaid coverage (compared to commercial insurance), were less likely to undergo a minimally invasive surgical approach (p<0.05). The median OS was 28 months (95% CI: 23.7-30.7) and 24.3 months (95% CI: 22.3-26.1) for MIS and laparotomy, respectively. After propensity score balancing, there was no association between the use of MIS and overall survival (HR: 0.90, 95% CI: 0.71-1.14). Conclusions: Among women with stage IV uterine cancer treated with neoadjuvant chemotherapy, the performance of minimally invasive debulking surgery is common and increasing. Compared to laparotomy, MIS does not appear to negatively impact survival. Objectives: The utilization of neoadjuvant chemotherapy (NACT) for advanced-stage uterine cancer is increasing. However, the relationship between NACT administration and the type of surgical approach used for interval debulking surgery (IDS) remains unknown. We analyzed the use and outcomes of open versus minimally invasive surgery (MIS) for women with stage IV uterine cancer who received NACT and underwent IDS. Methods: The National Cancer Database was used to identify women with stage IV uterine cancer diagnosed from 2010 to 2017 and treated with NACT. Among women who underwent IDS, overall survival (OS) was compared between those who underwent laparotomy versus a minimally invasive approach. To account for imbalances in confound- ers, a propensity score analysis using inverse probability of treatment weighting (IPTW) was performed. Cox proportional hazards models to compare all-cause mortality between the groups were examined. Results: A total of 1,618 women with stage IV uterine cancer who received NACT were identified. Overall, minimally invasive IDS was performed in 31.1% of the cohort. MIS use increased from 16.2% in 2010 to 40.4% in 2017 (p<0.001). More recent years of diagnosis and performance of surgery at a comprehensive cancer center or integrated network cancer center were associated with increased use of MIS (p<0.05). Women with serous and clear cell tumors and carcinosarcomas (compared to endometrioid tumors), as well as Medicaid coverage (compared to commercial insurance), were less likely to undergo a minimally invasive surgical approach (p<0.05). The median OS was 28 months (95% CI: 23.7-30.7) and 24.3 months (95% CI: 22.3-26.1) for MIS and laparotomy, respectively. After propensity score balancing, there was no association between the use of MIS and overall survival (HR: 0.90, 95% CI: 0.71-1.14). Conclusions: Among women with stage IV uterine cancer treated with neoadjuvant chemotherapy, the performance of minimally invasive debulking surgery is common and increasing. Compared to laparotomy, MIS does not appear to negatively impact survival.

Therapeutic effects of Vernonia amygdalina on the expression of hormone and HER2 receptors in 7, 12-dimethylbenz(a)anthracene-induced breast tumours in obese and non-obese Wistar rats

BackgroundObesity, a risk factor for breast cancer has been shown to be associated with poor response to neoadjuvant chemotherapy in women with breast cancer. Medicinal plants have been used to treat chronic diseases like cancer with little or no side effects. Vernonia amygdalina (VA) is a medicinal plant with anticancer activity. Previous studies on the anticancer potential of V. amygdalina against breast cancer are however entirely in vitro studies. The efficacy of V. amygdalina on obesity-associated breast cancer has also not been investigated in previous studies. This study explored VA’s anti-cancer effects on obesity- and non-obesity-associated 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast tumours in Wistar rats (WRs). MethodThirty female obese and non-obese WRs were studied, each group divided into six subgroups of five. At the 7th postnatal week (p.w), three subgroups were given a subcutaneous injection of DMBA to the breast with two of these three subgroups also commenced on daily oral VA at 250 mg/kg and 500 mg/kg from the 9th p.w. Same doses of VA were administered to two of the subgroups that did not receive DMBA while the last subgroup was placed on placebo from the 9th p.w. Haematoxylin and eosin staining were carried out on the excised breast tumours to evaluate general histoarchitecture, while immunohistochemistry was done for oestrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER2) expression. ANOVA and Mann-Whitney followed by posthoc tests were used to analyse the data. Alpha level was set at 0.05. ResultsWhile the DMBA-induced tumours were triple-negative in the obese WRs, they were ER, PR HER2-positive in the non-obese group. Vernonia amygdalina was associated with a reduction in cancer cell proliferation in both obese and non-obese groups despite the differences in immunohistochemical profiles of the tumours. Vernonia amygdalina was associated with reversal of the increased ER, PR and HER2 expressions in the breast tumours of the non-obese rats. ConclusionsConclusively, VA had more therapeutic effects on DMBA-induced breast tumours in the non-obese than obese WRs.

Value of shear wave elasticity in predicting the efficacy of neoadjuvant chemotherapy in different molecular types

PurposeThe purpose of this study was to evaluate the response to neoadjuvant chemotherapy (NAC) of different molecular subtypes of breast cancer using shear wave ultrasound elastography (SWE). MethodsNinety-eight patients with final diagnoses of breast cancer prior to NAC were examined with SWE and B-mode ultrasound. These parameters were compared with the response evaluation criteria in solid tumors (RECIST) index and pathological diagnoses. Then, we recorded the area under the receiver operating characteristic (ROC) curve. Immunohistochemical markers, including estrogen receptor (ER), progesterone receptor (PR), Ki67 index, and human epidermal growth factor receptor 2 (HER2) score, were examined before neoadjuvant treatment. Then, the diagnostic efficacy of SWE in different molecular subtypes was evaluated. ResultsOne-way analysis of variance revealed that age, tumor margin, the change in tumor size after chemotherapy, and the average (Emean), minimum (Emin), and maximum (Emax) values from shear wave elastography ultrasound before chemotherapy were related to the RECIST index. Multivariate regression revealed that age, tumor margin, the change in tumor size after chemotherapy, and Emax were independently correlated with the RECIST index. According to the ROC curve, the area under the curve (AUC) of Emax was 0.773. The AUC of Emean, Emin, and the ratio between tumor tissue and normal tissue (EI) were 0.630, 0.617, and 0.510, respectively. The Emax, Emin, Emean, and EI before and after NAC were significantly different (p ≤ 0.05). There was statistical significance in Luminal B type and HER2 enriched type in correlation results of the Emax values and RECIST indexes of different molecular subtypes. However, there was no significant difference in the Luminal A type and Triple negative types. There was no significant difference in the Emax values before NAC between the pathologic complete response (pCR) group and the non-pCR group (p > 0.05). ConclusionEmax can be used to predict the response to NAC in women with invasive breast cancer, especially those with the Luminal B type and HER2 enriched type, but it cannot be used to predict pCR to NAC.

Fertility-sparing surgery after neo-adjuvant chemotherapy in women with cervical cancer larger than 4 cm: a systematic review

ObjectiveThe objective of this systematic review was to assess the oncologic and fertility outcomes of patients with cervix-confined cancer >4 cm who underwent neo-adjuvant chemotherapy followed by fertility-sparing surgery.MethodsThis study...

Impact of prehabilitation during neoadjuvant chemotherapy and interval cytoreductive surgery on ovarian cancer patients: a pilot study

BackgroundCytoreductive surgery followed by systemic chemotherapy is the standard of treatment in advanced ovarian cancer where feasible. Neoadjuvant chemotherapy (NACT) followed by surgery is applicable where upfront cytoreductive surgery is not feasible because of few certain reasons. Nevertheless, surgical interventions and the chemotherapy itself may be associated with postoperative complications usually entailing slow postoperative recovery. Prehabilitation programs consist of the patient’s preparation before surgery to improve the patient’s functional capacity. The aim of this study was to evaluate the impact of a prehabilitation program during neoadjuvant treatment and interval cytoreductive surgery for ovarian cancer patients.MethodsA retrospective observational pilot study of patients with advanced ovarian cancer treated with NACT and interval cytoreductive surgery was conducted. The prehabilitation group received a structured intervention based on physical exercise, nutritional counseling, and psychological support. Nutritional parameters were assessed preoperatively and postoperatively, and functional parameters and perioperative and postoperative complications were also recorded.ResultsA total of 29 patients were included in the study: 14 in the prehabilitation group and 15 in the control group. The patients in the prehabilitation program showed higher mean total protein levels in both preoperative (7.4 vs. 6.8, p = 0.004) and postoperative (4.9 vs. 4.3, p = 0.005) assessments. Up to 40% of controls showed intraoperative complications vs. 14.3% of patients in the prehabilitation group, and the requirement of intraoperative blood transfusion was significantly lower in the prehabilitation group (14.3% vs. 53.3%, p = 0.027). The day of the first ambulation, rate of postoperative complications, and length of hospital stay were similar between the groups. Finally, trends towards shorter time between diagnosis and interval cytoreductive surgery (p = 0.097) and earlier postoperative diet restart (p = 0.169) were observed in the prehabilitation group.ConclusionPrehabilitation during NACT in women with ovarian cancer candidates to interval cytoreductive surgery may improve nutritional parameters and thereby increase postoperative recovery. Nevertheless, the results of this pilot study are preliminary, and further studies are needed to determine the clinical impact of prehabilitation programs.

Adoption of minimally invasive surgery after neoadjuvant chemotherapy in women with metastatic uterine cancer

ObjectiveUtilization of neoadjuvant chemotherapy (NACT) for advanced stage uterine cancer is increasing. We analyzed the use and outcomes of open versus minimally invasive surgery (MIS) for women with stage IV uterine cancer who received NACT and underwent IDS. MethodsThe National Cancer Database was used to identify women with stage IV uterine cancer diagnosed from 2010 to 2017 and treated with NACT. Among women who underwent IDS, overall survival (OS) was compared between those who underwent laparotomy vs a minimally invasive approach. To account for imbalances in confounders, a propensity score analysis using inverse probability of treatment weighting (IPTW) was performed. ResultsA total of 1618 women were identified. Minimally invasive IDS was performed in 31.1% and increased from 16.2% in 2010 to 40.4% in 2017 (P < 0.001). More recent year of diagnosis and performance of surgery at a comprehensive cancer center were associated with increased use of MIS (P < 0.05). Women with serous and clear cell tumors, and carcinosarcomas (compared to endometrioid tumors), as well as Medicaid coverage (compared to commercial insurance) were less likely to undergo an MIS approach (P < 0.05). The median OS was 28 months (95% CI 23.7–30.7) and 24.3 months (95% CI 22.3–26.1) for MIS and laparotomy, respectively. After propensity score balancing, there was no association between the use of MIS and survival (HR = 0.90, 95% CI 0.71–1.14). ConclusionsAmong women with stage IV uterine cancer treated with NACT performance of minimally invasive debulking surgery is increasing. Compared to laparotomy, MIS does not appear to negatively impact survival.

P–455 Breast cancer recurrence in women with and without controlled ovarian stimulation for fertility preservation. Cohort study

Abstract Study question Do patients diagnosed with breast cancer who undergo ovarian stimulation for fertility preservation prior to chemotherapy have a higher risk of recurrence of the disease? Summary answer There was no statistically significant difference in the hazard ratio for breast cancer recurrence in fertility preservation-stimulated women compared to non-stimulated ones What is known already While many women with early breast cancer benefit from chemotherapy treatments in increasing disease-free survival, they are also at risk of permanent chemotherapy induced ovarian failure. Oocyte cryopreservation with an adapted protocol with letrozole may reduce the possible deleterious effect of the hyper estrogenic state during the controlled ovarian hyperstimulation (COH). Although fertility preservation in women diagnosed with breast cancer seems safe, the follow-up periods of most studies are short in time. In addition, follow-up data of COH before neoadjuvant chemotherapy in women with hormone negative tumor receptors is still scarce and briefly reported. Study design, size, duration It was a retrospective cohort study, where 208 women with non-metastatic breast cancer were included. The recruitment period was from 01/01/2009 to 01/12/2019. The minimum follow-up period was 6 months, and the maximum, 130 months. Participants were divided into two cohorts, those who received controlled ovarian hyperstimulation prior to their cancer treatment and those who did not. Patients were followed until disease recurrence, death, loss to follow-up, or end of the study Participants/materials, setting, methods Setting: university hospital in Buenos Aires, Argentina. We included women aged 18 to 45 years with a recent histological diagnosis of non-metastatic breast cancer who had to receive chemotherapy with gonadal toxicity. We excluded patients with a history of previous chemotherapy or radiotherapy for another cancer disease, or menopause. Follow-up was at least an annual clinical check-up and breast imaging. Cohorts were analysed using a Cox-proportional hazards model, adjusted for propensity score for receiving stimulation. Main results and the role of chance We included 208 women, 39 in the COH group and 169 in the non-stimulated group (NSG). The only statistically significant difference was in age: median years 33.7 (interquartile range -IQR- 30.9 to 36.9) and 40.0 years (IQR 36.8 to 44.0), respectively. The median size of cancer nodules was 19.0 millimetres (IQR 10.0–30.0) and 17.0 (IQR 11.0–25.0), p 0.547; percentage of positive lymph nodes: 41.0% vs 39.3%, p 0.841; positive hormonal receptors: 84.6% vs 85.2%, p 0.925; percentage of neoadjuvant chemotherapy: 20.5% vs 11.4%, p 0.128. There were also no statistically significant differences regarding tumour stage, high Ki–67 labelling index, positive breast cancer genes (BRCA 1 or 2), and radiotherapy. Overall, 18.0% of patients had cancer recurrence in the COH group and 20.7% in the NSG (p 0.699). Crude cancer recurrence rates were similar: 5.96 per 100 patients/year (95%CI 2.84–12.50), and 4.65 per 100 patients/year (95%CI 3.34–6.47), respectively. The crude hazard ratio (HR), comparing the COH group vs the NSG was 1.32 (95%CI 0.58–2.97; p 0.507). The adjusted HR using a propensity score for receiving ovarian stimulation treatment was 1.08 (95%CI 0.39–2.98; p 0.887). Results were similar if adjusted for age, neoadjuvant chemotherapy, and other confounders. Limitations, reasons for caution This was a single-center retrospective cohort study. There might be unknown or residual confounders that could influence results. Nevertheless, we accounted for treatment bias using a propensity score for ovarian stimulation. Results should be extrapolated with caution, especially in other non-university institutions and populations. Wider implications of the findings: This study provides new evidence on the safety of controlled ovarian stimulation in breast cancer patients prior to chemotherapy treatment, in a Latin American population. Letrozole continues to show safety and efficacy as an adapted protocol in breast cancer. Trial registration number Not applicable

A multi-institutional study of minimally invasive surgery compared to laparotomy for interval debulking after neoadjuvant chemotherapy in women with advanced ovarian cancer

<h3>Objectives:</h3> Neoadjuvant chemotherapy (NAC) is becoming more ubiquitous for treatment of advanced epithelial ovarian cancer (EOC), and mode of interval debulking surgery (IDS) has not been adequately evaluated. A minimally invasive surgical (MIS) approach offers several advantages to an open approach (O-IDS), especially in the current COVID-19 pandemic, but data regarding outcomes are limited. We sought to compare the surgical and oncologic outcomes of MIS and O-IDS in patients (pts) with advanced EOC. <h3>Methods:</h3> All consecutive patients with stages III to IV EOC who underwent NAC followed by IDS from 2008-2018 at 3 tertiary care centers were included in this retrospective cohort study. Demographic, clinical, and pathologic factors were abstracted from electronic medical records. Progression-free survival (PFS) and overall survival (OS) were analyzed on a Kaplan-Meier estimator using the log-rank method, and Cox proportional hazards regression models were used for univariate and multivariate survival analyses. <h3>Results:</h3> A total of 415 pts underwent IDS through MIS (n=122; robotic=78, laparoscopic=44), or O-IDS (n=293). There were no statistically significant differences between age at diagnosis (O-IDS 63.2, MIS 65.3; p=0.1), stage (p=0.3), and grade (p=0.06). There were also no differences between CA-125 levels measured at diagnosis (O-IDS 3145 U/mL, MIS 2247 U/mL; p=0.2) or after completion of NACT (O-IDS 251.7 U/mL, MIS 179.1 U/mL; p=0.4) between the 2 groups. MIS was completed without conversion in 84 of 122 patients (68.8%), with most conversions occurring in the robotic group. Patients undergoing MIS had significantly fewer complex surgeries, with 81% of the cases categorized as low complexity when scored using the Aletti SCS, compared to 64% of open surgeries (p<0.001). Patients undergoing open surgeries had significantly higher estimated blood loss (EBL; 326.2cc vs 181.5cc; p<0.001) and intraoperative transfusion rate (25% vs 4%; p<0.001). These patients also had a longer hospital length of stay (5.9 days vs 2.2 days; p<0.001) as well as 30-day postoperative complication rate (43% vs 20%, p<0.001). There were no observed differences between the 2 groups in terms of operative time (191.1 minutes vs 196.3 minutes; p=0.5) and 30-day hospital readmission rates (10% vs 6%; p=0.2). With regard to surgical cytoreduction, patients undergoing MIS had significantly higher rates of both R0 (66% vs 46%; p<0.001) and optimal, or R0/R1 (93% vs 84%; p=0.02) debulking rates. Patients undergoing open surgery trended towards having a higher rate of recurrence at 24 months after diagnosis, but this difference did not reach significance (70% vs 60%; p=0.06). Finally, there were no differences in the 2 groups in terms of PFS or OS (Figure 2). Median PFS was 15.1 months for O-IDS and 18.2 months for MIS (p=0.051). Median OS was 36.7 months for O-IDS and 40.9 months for MIS (p=0.5). <h3>Conclusions:</h3> MIS is a feasible and potentially effective mode of IDS after NAC in patients with advanced EOC. Surgical outcomes appear to be advantageous in MIS compared with O-IDS, and oncologic outcomes appear to be no different. Further investigation of robotic MIS compared with laparoscopic MIS for IDS is warranted.

The correlation between BRCA status and surgical cytoreduction in high-grade serous ovarian carcinoma

<h3>Objectives:</h3> BRCA-associated ovarian cancers are biologically unique, as evident by differential molecular and clinical behaviour of these tumor as compared to sporadic ovarian cancers. It is unclear if these biological differences translate to favorable outcomes at the time of primary cytoreduction. The aim of this study is to compare the amount of residual disease after primary cytoreduction in <i>BRCA</i> mutated and wildtype populations, and to assess whether <i>BRCA</i> status is an independent predictor of optimal cytoreduction. <h3>Methods:</h3> We conducted a retrospective analysis of patients with high-grade serous (HGSC) ovarian cancers with known germline and somatic <i>BRCA</i> mutation status, treated with primary cytoreductive surgery from 2000 to 2017. Post-operative <i>BRCA</i> germline and somatic testing was conducted in all cases. We compared the complete, optimal and suboptimal cytoreduction rates between the <i>BRCA</i> positive and the <i>BRCA</i> negative cohorts and built a predictive model to assess whether the <i>BRCA</i> status was associated with the amount of residual disease after controlling for confounding variables. <h3>Results:</h3> Of 355 women with HGSC ovarian cancers treated with primary cytoreduction, 144 harbored germline or somatic <i>BRCA</i> mutations (41%) and 211 were <i>BRCA</i> wildtype (59%). <i>BRCA</i> positive women tended to be younger (54 vs 59; p<0.001), but there were no differences between the two groups in preoperative CA-125 levels, disease burden (measured by disease score), surgical complexity score, stage distributions, length of surgery, intraoperative or postoperative complications. Comparing residual disease burden at the end of primary cytoreduction, the <i>BRCA</i> positive group had a higher rate of complete cytoreduction to no residual disease (0mm) [75% vs 54%], and a lower rate of optimal cytoreduction (1-9mm) [16% vs 34%] or suboptimal cytoreduction (≥10mm) [9% vs. 12%] (p<0.001). In our predictive model, after accounting for length of surgery, CA-125 level, stage distributions, disease scores and surgical complexity scores, <i>BRCA</i> positive status was predictive of complete cytoreduction to 0mm residual disease with odds ratio (OR) of 4.78 (95% CI 2.32-9.85; p<0.001). Subgroup analysis restricted to patients with stage III/IV HGSC showed similar results, with <i>BRCA</i> positive status having OR of 5.2 (95% CI 2.44-11.09; p<0.001) for complete primary cytoreduction. <h3>Conclusions:</h3> <i>BRCA</i> status is predictive of complete and optimal cytoreduction at the time of primary surgical cytoreduction in patients presenting with newly diagnosed ovarian cancer. This positive correlation should be taken into consideration when deciding between primary cytoreductive surgery or neoadjuvant chemotherapy in women with this disease.

Radiological and pathological assessment of response to neoadjuvant CDK4/6 inhibitor and endocrine treatments in a real-life setting-initial results.

BackgroundNeoadjuvant endocrine therapy is an alternative to neoadjuvant chemotherapy in women with inoperable luminal-like breast cancers. Neoadjuvant cyclin-dependent kinase 4/6 inhibitor treatment combined with endocrine treatment (CDK4/6I + E) is interesting given the combination’s utility in the treatment of metastatic breast cancer. Currently, the literature on the radiological response evaluation of patients treated with neoadjuvant CDK4/6I + E in a real-life setting is scarce.PurposeTo conduct a radiological response evaluation of patients treated with neoadjuvant CDK4/6I + E in a real-life setting.Material and methodsWe retrospectively reviewed clinical, pathological, and radiological findings of six patients with luminal-like breast cancers treated with neoadjuvant CDK4/6I + E treatment. The radiological neoadjuvant CDK4/6I + E response was evaluated with the RECIST 1.1 criteria and the pathological residual disease was assessed using the Residual Cancer Burden (RBC) criteria.ResultsNone of the patients achieved a complete radiological magnetic resonance imaging (MRI)–determined response or a complete pathological response; three (50%) patients had a partial radiological response; in the three others, the disease remained stable radiologically. All of the tumors were rendered susceptible to surgical treatment. Two out of six (33.3%) patients had a moderate response (RBC-II); four (66.7%) had an extensive residual disease (RBC-III) in the final surgical sample.ConclusionAlthough none of the patients achieved a pathologically complete response, neoadjuvant CDK4/6I + E treatment rendered all tumors operable. MRI appears to be reliable in the assessment of the neoadjuvant CDK4/6I + E treatment response in a real-life setting. Larger studies are warranted to confirm these results.

The correlation between BRCA status and surgical cytoreduction in high-grade serous ovarian carcinoma.

5543 Background: High grade serous ovarian cancers (HGSC) with BRCA mutation are biologically unique, with distinct molecular and clinical behaviour from sporadic cases. It is unclear if these biological differences translate to favorable outcomes at the time of primary cytoreductive surgery (PCS). The aim of this study is to compare the amount of residual disease following PCS in BRCA-mutated (BRCAm) and wildtype (BRCAwt) HGSC, and to assess whether BRCA status is an independent predictor of residual disease. Methods: We conducted a retrospective analysis of patients with HGSC with known germline and somatic BRCA mutation status, treated with PCS from 2000 to 2017. We compared the cytoreduction outcomes between the BRCAm and the BRCAwt cohorts and built a predictive model to assess whether BRCA status was associated with amount of residual disease at the time of PCS. Results: Of 355 women, 144 harbored germline or somatic BRCA mutations (41%) and 211 were BRCAwt (59%). BRCAm women tended to be younger (54 vs. 59; p &lt; 0.001), but there were no differences between the two groups in stage, disease burden at presentation, surgical complexity score, length of surgery, or perioperative complications. The BRCAm group had a higher rate of complete cytoreduction to no residual disease (0mm) [75% vs. 54%], and a lower rate of optimal cytoreduction (1-9mm) [16% vs. 34%] or suboptimal cytoreduction (≥10mm) [9% vs. 12%] (p &lt; 0.001). In our predictive model, after accounting for length of surgery, CA-125 level, stage, disease scores and surgical complexity scores, BRCAm status was predictive of complete cytoreduction to 0mm residual disease (OR 4.78; 95% CI 2.32-9.85; p &lt; 0.001). Conclusions: BRCA status is predictive of complete cytoreduction at time of PCS in HGSC. Timely availability of BRCA testing is paramount as it may aid in the therapeutic decision making between PCS or neoadjuvant chemotherapy in women with newly diagnosed HGSC.

Radical Hysterectomy With and Without Neoadjuvant Chemotherapy in Patients With Cervical Cancer Stage IB-IIB

Objectives: In this study, radical hysterectomy, followed by neoadjuvant chemotherapy (NACT) in patients with locally advanced cervical cancer (LACC) was compared with radical hysterectomy in patients with early-stage cervical cancer. Material and Methods: This retrospective comparative observational study was performed on 13 patients with LACC International Federation of Gynecology and Obstetrics (FIGO) stage IB2-IIB who underwent a radical hysterectomy after NACT between March 2014 and November 2018. This group was compared with 18 patients undergoing radical hysterectomy with cervical cancer FIGO stage IIA-IB1 in the same period of time. Results: In the NACT group, 8 (61.5%) and 5 (38.4%) patients were in stages IIB and IB2, respectively, and 13 (72.2%) cases were in the IB1 stage in the non-NACT group. Post-operative blood transfusion in the NACT group was significantly higher compared to the non-NACT group [5 (38.4%) patients versus 0, P = 0.008]. The estimated blood loss (EBL) and operative time were similar between the groups. Finally, there were no significant differences in terms of intra-operative and other post-operative complications. Conclusions: Radical hysterectomy after NACT in women with LACC seems to be safe and reduces the need for radiation in patients with NACT who are at stage IIB. These results need to be confirmed in studies with a larger patient sample.