Systemic Treatment Of Breast Cancer Research Articles

Alisol A is potentially therapeutic in human breast cancer cells.

Recent developments in breast cancer therapy have significantly improved patient survival rate; however, recurrence remains a major problem. Systemic treatment of breast cancer with available therapies is not curative. Natural products can be potentially used for treating cancer. Recently, a wide range of pharmacological activities has been reported for Alismatis Rhizoma, a popular traditional Chinese medicine. However, the mechanisms via which its compounds act on breast cancer remain unclear. The present study aimed to investigate the potential of natural therapeutic agents from Alismatis Rhizoma for treating breast cancer. Human breast cancer MDA‑MB‑231 cells were treated with four main protostane triterpenes from Alismatis Rhizoma, including alisol A, alisol A 24‑acetate, alisol B and alisol B 23‑acetate. Among these, alisol A significantly inhibited cell viability. AlisolA induced cell apoptosis, G1 phase cell cycle arrest, autophagy, and intracellular reactive oxygen species (ROS) generation in MDA‑MB‑231 cells. The number of APE1‑/γH2AX‑/LC3‑II positive cells was also significantly higher compared with that of negative control cells. All these results were dose‑dependent. Cleaved caspase‑3, cleaved caspase 9, Bcl‑2, and p‑p38 expression indicated cell apoptosis after alisol A treatment. The changes in cyclin A and cyclin D1 expression was associated with cell cycle arrest upon alisol A treatment. Furthermore, LC3‑II expression upon alisol A treatment was indicative of autophagy. Alisol A treatment can induce autophagy‑dependent apoptosis in human breast cancer cells via induction of ROS and DNA damage. Thus, Alisol A might serve as a new therapeutic agent against breast cancer.

Utilization of the Cancer Medications Enquiry Database (CanMED)-National Drug Codes (NDC): Assessment of Systemic Breast Cancer Treatment Patterns

Cancer Medications Enquiry Database (CanMED) is comprised of two interactive, nomenclature-specific databases within the Observational Research in Oncology Toolbox: CanMED-Healthcare Common Procedure Coding System (HCPCS) and CanMED-National Drug Code (NDC), described through this study. CanMED includes medications with a) a US Food and Drug Administration-approved cancer treatment or treatment-related symptom management indication, b) inclusion in treatment guidelines, or c) an orphan drug designation. To demonstrate the joint utility of CanMED, medication codes associated with female breast cancer treatment were identified and utilization patterns were assessed within Surveillance Epidemiology and End Results-Medicare (SEER) data. CanMED-NDC (11_2018 v.1.2.4) includes 6860 NDC codes: chemotherapy (1870), immunotherapy (164), hormone therapy (3074), and ancillary therapy (1752). Treatment patterns among stage I-IIIA (20701) and stage IIIB-IV (2381) breast cancer patients were accordant with guideline-recommended treatment by stage and molecular subtype. CanMED facilitates identification of medications from observational data (eg, claims and electronic health records), promoting more standardized and efficient treatment-related cancer research.

Systemic treatment of breast cancer with leptomeningeal metastases using bevacizumab, etoposide and cisplatin (BEEP regimen) significantly improves overall survival

IntroductionMetastatic breast cancer (MBC) with leptomeningeal metastases (LM) has dismal survival. We aim to determine if modern systemic therapy, especially the bevacizumab, cisplatin, and etoposide (BEEP) regimen, is beneficial to MBC LM patients.MethodsWe excerpted data from a prospectively collected cytopathology database for MBC patients who were diagnosed with LM by positive cerebrospinal fluid cytology. The primary outcome was OS from cytologically confirmed LM until death. Univariate and multivariate analyses were performed to elucidate prognostic factors.ResultsWe identified 34 patients with cytologically confirmed LM. Treatments after LM diagnosis included: intrathecal methotrexate (82.4%), systemic chemotherapy (68%; BEEP n = 19, others n = 4), and whole brain radiotherapy (n = 5, 14.7%). Three of seven HER2-positive patients (43%) also received intrathecal trastuzumab. OS was improved in 2014–2016 compared with 2011–2013 (13.57 vs 3.20 months, p = 0.004), when 12/17 (71%) versus 7/17 (41%) patients received BEEP, respectively. In the multivariate model including all treatments, BEEP (HR 0.24, p = 0.003) and intrathecal trastuzumab (HR 0.22, p = 0.035), but not intrathecal methotrexate (HR 0.86, p = 0.78), remained significant prognostic factors.ConclusionsMBC with LM is treatable—systemic BEEP are efficacious and may improve survival.

The Japanese Breast Cancer Society Clinical Practice Guidelines for systemic treatment of breast cancer, 2018 edition

PurposeWe present the English version of The Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for systemic treatment of breast cancer, 2018 edition.MethodsThe JBCS formed a task force to update the JBCS Clinical Practice Guidelines, 2015 edition, according to Minds Handbook for Clinical Practice Guideline Development 2014. First, we set multiple outcomes for each clinical question (CQ). Next, quantitative or qualitative systematic review was conducted for each of the multiple outcomes, and the strength of recommendation for the CQ was taken into consideration during meetings, with the aim of finding a balance between benefit and harm. Finalized recommendations from each session were confirmed through discussion and voting at the recommendation decision meeting.ResultsThe recommendations, the strength of recommendation and the strength of evidence were determined based on systemic literature reviews and the meta-analyses for each CQ.ConclusionThe JBCS updated the Clinical Practice Guidelines for systemic treatment of breast cancer.

General recommendations for the management of breast cancer (St. Gallen Expert Consensus developed at the 16<sup>th </sup>th International Breast Cancer Conference)

This article summarizes the results of the 16th St. Gallen International Breast Cancer Conference (March 2019), which traditionally resulted in the development of a new guideline for local/regional and systemic treatment of breast cancer.

WDR5 inhibition halts metastasis dissemination by repressing the mesenchymal phenotype of breast cancer cells

BackgroundDevelopment of metastases and drug resistance are still a challenge for a successful systemic treatment in breast cancer (BC) patients. One of the mechanisms that confer metastatic properties to the cell relies in the epithelial-to-mesenchymal transition (EMT). Moreover, both EMT and metastasis are partly modulated through epigenetic mechanisms, by repression or induction of specific related genes.MethodsWe applied shRNAs and drug targeting approaches in BC cell lines and metastatic patient-derived xenograft (PDX) models to inhibit WDR5, the core subunit of histone H3 K4 methyltransferase complexes, and evaluate its role in metastasis regulation.ResultWe report that WDR5 is crucial in regulating tumorigenesis and metastasis spreading during BC progression. In particular, WDR5 loss reduces the metastatic properties of the cells by reverting the mesenchymal phenotype of triple negative- and luminal B-derived cells, thus inducing an epithelial trait. We also suggest that this regulation is mediated by TGFβ1, implying a prominent role of WDR5 in driving EMT through TGFβ1 activation. Moreover, such EMT reversion can be induced by drug targeting of WDR5 as well, leading to BC cell sensitization to chemotherapy and enhancement of paclitaxel-dependent effects.ConclusionsWe suggest that WDR5 inhibition could be a promising pharmacologic approach to reduce cell migration, revert EMT, and block metastasis formation in BC, thus overcoming resistance to standard treatments.

212P - The rationale for the effectiveness of systemic treatment of breast cancer depending on the body weight index

BackgroundBreast cancer in the world in general and in Ukraine is steadily increasing. Epidemiological, experimental and clinical studies have shown that metabolic disturbances associated with BMI> 30kg / m2 increase the risk of occurrence and worsen the clinical course of breast cancer. Thus, in patients with obesity, a decrease in the sensitivity of the tumor to systemic antitumor therapy, an increase in the frequency of postoperative complications and a decrease in the rates of general and non-recurrent survival. MethodsThe aim of the study was to improve the results of neoadjuvant systemic antitumor therapy in breast cancer patients with abdominal obesity (BMI greater than 30kg / m2) by administering levocarnitine in combination with neoadjuvant systemic anticancer therapy (NSAT) for the correction of metabolic disorders as the main pathogenetic part of obesity. Following randomization of all patients (n=108) with breast cancer with BMI> 30kg / m2, depending on the appointment of levocarnitine during NSAT, were divided into 2 groups: comparison and observation. In the comparison group, patients (n=58) with BMI> 30kg / m2 patients with breast cancer who did not receive levocarnitine during NSPT, and in the, observation group - patients (n=50) on breast cancer with BMI> 30kg / m2 who received levocarnitine during NIST ResultsAfter neoadjuvant systemic anticancer therapy, regardless of the purpose levocarnitine decreased residual tumor cell proliferation index (Ki-67) and increased incidence of Luminal A molecular type of breast cancer. Against neoadjuvant systemic anticancer therapy for breast cancer patients with a BMI over 30kg / m2 to be additionally administered drugs that increases the incidence of complete morphological regression. This drug is levocarnitine in therapeutic doses (1500mg / day), which has proven to be an effective means to increase the number of cases of clinically relevant responses (CR + PR) to the treatment. ConclusionsLevocarnitine contributes to an increase in the number of cases of objective clinical (complete regression and partial regression) and morphological (therapeutic pathomorphosis IV and V degree) tumor response to cytotoxic breast cancer therapy in patients with BMI> 30kg / m2 and frequency of organ-saving surgical interventions. Legal entity responsible for the studyThe author. FundingHas not received any funding. DisclosureThe author has declared no conflicts of interest.

Physiological and psychosocial effects of a highly structured exercise program on breast cancer survivorship.

11558 Background: Exercise after breast cancer treatment improves cancer-related outcomes, although the mechanism of action is unclear. Engagement in healthy active lifestyles after cancer treatment may also impact overall survival. We aimed to determine effectiveness of a highly structured, clinically overseen, goal oriented, group triathlon training program on improving physiological and psychosocial outcomes in female breast cancer survivors (BCS). Methods: After stage appropriate local and systemic breast cancer treatment, 53 female BCS were recruited to participate in this study. The 14-week group triathlon training program was individually adjusted for treatment side effects. 28 similar BCS who did not participate in the training served as controls. Pre- and post-exercise training measures included: Functional endurance (Timed 6MWT), quality of life (QOL, FACT-B), cancer-related fatigue (CRF, FACIT-F), exercise self-efficacy (ESE) via questionnaires, estradiol, and inflammatory biomarkers (C-reactive protein, TNFr1, leptin and adiponectin). Results: Complete data were obtained from 41 [mean age 51 (7) yr, mean BMI 29.5 (6.2)] triathlon finishers and 16 [mean age 56 (10) yr, mean BMI 31.5 (8.0)] controls. 6MWT improved (26 m) more in the triathlon group (p < 0.05). FACT-B, FACIT-F, and ESE all improved compared to controls (all p < 0.05). Body mass and BMI decreased in the training group compared to controls (p = 0.01, p = 0.04 respectively). Arm circumference decreased in the trained group but increased in controls (p < 0.05). Estradiol and leptin positively correlated with initial body weight in both groups but did not change after training. Adiponectin significantly decreased in the triathlon group (p = 0.01), perhaps due to selection bias of controls. No significant changes were seen in other serological markers. Conclusions: A highly structured, clinically overseen, moderate intensity exercise program can improve endurance, QOL, CRF, body mass, and possibly improve survival after breast cancer treatment. Furthermore, improvements in ESE may provide tools for patients to continue adherence to regular exercise guidelines that may lower obesity and its related comorbidities, including arm lymphedema.

Abstract P5-13-11: Impact of public health insurance “Seguro Popular” on breast cancer recurrence at Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico City

Abstract Introduction. Public health insurance called Seguro Popular (SP) for breast cancer treatment (BCT) was instituted in Mexico in 2007. Our third level center was enrolled until 2011. SP covers systemic BCT (WHO 20th model list essential medicines). The aims were: 1) Describe frequency and type of breast cancer recurrence (BCR), 2) compare which factors were contributing to recurrence of breast cancer patients (pts) before and after the implementation of SP. Methods. Pts with diagnosis of breast cancer (BC) from 2004 to 2018 were analyzed and pts with BCR whom primary tumor (PBC) was treated and followed at INCMNSZ were recruited. They were divided into two groups according to access to SP: pts without Seguro Popular (non-SP) and, pts with SP. Xi-square, non-parametric tests and Kaplan-Meier curves (log-rank test) were used. Logistic regression was done for multivariate analysis. A p-value <0.05 was considered significant. Results. Between 2004 and 2018, 929 pts with BC were diagnosed; 438 non-SP and 473 SP. Ninety-one (9.7%) had a BCR (loco-regional or distant) during this period. Median follow-up was 125 months. The BCR proportion was higher within non-SP than in SP (74 (16.8%) vs 17 (3.5%) pts) (p=<0.05). Median age at diagnosis was higher in non-SP (p=0.028). Distant relapses were higher in non-SP than in SP (44 (59.4%) vs 8 (47%) pts). St Gallen 2017 Luminal A/B subtypes were most common in non-SP compared to SP where Basal-like subtype was higher (p=0.048). Luminal-A subtype had the best survival among non-SP compared to SP in which HER2 non-luminal had the higher survival (p<0.001). Conclusions. Experience with SP at our center shows promising results in the improvement of BCR. Access to adequate systemic management (hormone-blocking and HER2 targeted therapy) has a positive impact on recurrence, disease-free survival, and cancer-specific global survival. A longer follow-up time is required in the SP group (prospective cohort) to confirm these findings, especially in luminal tumors with late recurrence risk. Efforts should be made in the Mexican public health system to secure basic and continuous access to BCT. Citation Format: Mejía-Fernández L, Medina-Franco H, Armengol-Alonso A. Impact of public health insurance “Seguro Popular” on breast cancer recurrence at Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Mexico City [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-13-11.

Radioterapija nakon neoadjuvantnog sustavnog liječenja raka dojke

Radioterapija nakon neoadjuvantnog sustavnog liječenja raka dojke

Breast Health Global Initiative Recommended Breast Cancer Prevention and Care in Rural Ethiopia

Purpose Breast cancer is the most common cancer among women worldwide and is the leading cause of cancer death among women in low- and middle-income countries, including Ethiopia. Availability of both basic and comprehensive services in all frontline health care facilities is important for cancer control. Whereas women are equally affected in both urban and rural settings, most services are present in urban areas. We assessed health system readiness for breast cancer prevention and treatment in selected hospitals in Western Ethiopia. Methods A total of seven rural hospitals in Western Ethiopia were assessed for availability of comprehensive breast cancer services. A checklist prepared on the basis of breast care prevention and control standards for low-resource settings—recommended by the 2007 Global Summit of Breast Health Global Initiative—was used for the assessment. Data were descriptively analyzed and discussed. Results Whereas cancer incidence and mortality rates are increasing in Ethiopia and other sub-Saharan countries, there is currently no competent health system available that is adequately equipped to meet this challenge. In Ethiopia, the majority of systemic oncologic treatment is administered at the Addis Ababa University Hospital in the capital city, and the majority of patients are referred to this center, which, for the average patient, is more than 500 km away. There are relatively large numbers of health professionals in health facilities in Western Ethiopia, but a critical absence of pathologists and oncologists. Basic diagnostic services, such as ultrasonography and X-ray, were found to be available in most hospitals; however, there were major gaps in cytologic and pathologic services. The nearest referral centers for pathology and additional breast cancer treatment required travelling significant distances; there were no systemic breast cancer treatment and palliative services available in Western Ethiopia. Conclusion Our study revealed that all health facilities lack a comprehensive package of breast cancer diagnosis and treatment services. The lack of implemented comprehensive breast care prevention, diagnosis, treatment, and referral services is representative of most other rural settings in Ethiopia. This calls for a nationally coordinated effort in defining and implementing breast cancer prevention and control standards to realize the national cancer control plan. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc . Eva Kantelhardt Travel, Accommodations, Expenses: Daiichi Sankyo Oncology Europe

Long Non-Coding RNAs as New Master Regulators of Resistance to Systemic Treatments in Breast Cancer.

Predicting response to systemic treatments in breast cancer (BC) patients is an urgent, yet still unattained health aim. Easily detectable molecules such as long non-coding RNAs (lncRNAs) are the ideal biomarkers when they act as master regulators of many resistance mechanisms, or of mechanisms that are common to more than one treatment. These kinds of markers are pivotal in quasi-personalized treatment selection, and consequently, in improvement of outcome prediction. In order to provide a better approach to understanding development of disease and resistance to treatments, we reviewed current literature searching for lncRNA-associated systemic BC treatments including endocrine therapies, aromatase inhibitors, selective estrogen receptor modulators (SERMs), trastuzumab, paclitaxel, docetaxel, 5-fluorouracil (5-FU), anthracyclines, and cisplatin. We found that the engagement of lncRNAs in resistance is well described, and that lncRNAs such as urotelial carcinoma-associated 1 (UCA1) and regulator of reprogramming (ROR) are indeed involved in multiple resistance mechanisms, which offers tantalizing perspectives for wide usage of lncRNAs as treatment resistance biomarkers. Thus, we propose this work as the foundation for a wide landscape of functions and mechanisms that link more lncRNAs to resistance to current and new treatments in years of research to come.

Demographic, clinical and geographical factors associated with lack of receipt of recommended chemotherapy.

e13563Background: There have been significant advances in the systemic treatment of breast cancer over the past decade. Identifying factors associated with disparities in the receipt of chemotherap...

BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients.

BRCA1/2 mutations influence the molecular characteristics and the effects of systemic treatment of breast cancer. This study investigates the impact of germline BRCA1/2 mutations on pathological complete response and prognosis in patients receiving neoadjuvant systemic chemotherapy. Breast cancer patients were tested for a BRCA1/2 mutation in clinical routine work and were treated with anthracycline-based or platinum-based neoadjuvant chemotherapy between 1997 and 2015. These patients were identified in the tumor registry of the Breast Center of the University of Erlangen (Germany). Logistic regression and Cox regression analyses were performed to investigate the associations between BRCA1/2 mutation status, pathological complete response, disease-free survival, and overall survival. Among 355 patients, 59 had a mutation in BRCA1 or in BRCA2 (16.6%), 43 in BRCA1 (12.1%), and 16 in BRCA2 (4.5%). Pathological complete response defined as "ypT0; ypN0" was observed in 54.3% of BRCA1/2 mutation carriers, but only in 22.6% of non-carriers. The adjusted odds ratio was 2.48 (95% CI 1.26-4.91) for BRCA1/2 carriers versus non-carriers. Patients who achieved a pathological complete response had better disease-free survival and overall survival rates compared with those who did not achieve a pathological complete response, regardless of BRCA1/2 mutation status. BRCA1/2 mutation status leads to better responses to neoadjuvant chemotherapy in breast cancer. Pathological complete response is the main predictor of disease-free survival and overall survival, independently of BRCA1/2 mutation status.

Neoadjuvant systemic treatment for breast cancer in Italy: The Italian Society of Surgical Oncology (SICO) Breast Oncoteam survey

The Italian Society of Surgical Oncology (SICO) Breast Oncoteam developed a survey to explore the state of the art of neoadjuvant treatment for breast cancer in Italy, specifically focusing on cases treated during the two-year period 2014–2015.A questionnaire was sent to Italian Breast Units with a minimum of 150 new breast cancer cases treated/year according to the Senonetwork directory and to the SICO Breast Oncoteam Breast Unit network.A total of 23/107 Breast Units submitted the survey, reporting a total amount of 20156 cases of breast carcinoma (17241 invasive, 2915 in situ) treated in the biennium, corresponding approximately to 20% of newly diagnosed breast cancers in Italy.In the United States, medical treatment before surgery for breast cancer is indicated in about 22.7% of newly diagnosed cases according to the National Cancer Database, while a German study reported approximately 20% of cases treated with neoadjuvant therapy. In our survey, a total of 1673/17241 cases (9.7%) were treated with neoadjuvant therapy, ranging from 2.9% to 23.6% according to different centres, showing heterogeneity in neoadjuvant treatment indications, even in multidisciplinary breast units. Better resources should be engaged to achieve a standardised quality indicator for neoadjuvant treatment, and this indicator could be included among the European Society of Breast Cancer Specialists (EUSOMA) quality indicators. In the near future, we plan to develop a second survey to better test improvements in the employment of neoadjuvant therapy after the expiry of the 2016 European Parliament deadline and after the 2017 St. Gallen Conference recommendations.

335 (PB-130) - Identification and calculation of quality indicators in systemic treatment in breast cancer

335 (PB-130) - Identification and calculation of quality indicators in systemic treatment in breast cancer

Development of retargeted oHSV vectors for systemic treatment of breast cancer

Development of retargeted oHSV vectors for systemic treatment of breast cancer

Abundant tumor infiltrating lymphocytes after primary systemic chemotherapy predicts poor prognosis in estrogen receptor-positive/HER2-negative breast cancers.

The therapeutic effect of systemic treatment for breast cancer (BC) generally depends on its intrinsic subtypes. In addition, tumor infiltrating lymphocytes (TILs) are considered to be an independent factor for tumor shrinkage and disease prognosis. High TILs at baseline or after primary systemic chemotherapy are reported to be associated with better survival in triple-negative or human epithelial growth factor receptor 2 (HER2)-positive BCs. However, the prognostic value of TILs in estrogen receptor (ER)-positive and HER2-negative (ER+/HER2-) BC is still controversial. We assessed TIL score (low, intermediate, and high) before and after primary systemic chemotherapy in every subtype of BC, and compared the clinical outcomes. Biopsy specimens of 47 triple-negative, 58 HER2+ and 91 ER+/HER2- BCs were used to assess TILs before treatment. To assess TILs after treatment, we examined residual invasive carcinoma in surgically resected samples of 28 triple-negative, 30 HER2+ and 80 ER+/HER2- BCs. A high TIL score in triple-negative BC before treatment resulted in a significantly higher proportion of pathological complete response (pCR). In contrast, ER+/HER2- BC exhibited fewer instances of pCR than other subtypes. Although not statistically significant, ER+/HER2- cases with a high TIL score also tended to achieve pCR (p=0.088). Moreover, we revealed that low TIL BCs after chemotherapy, but not at baseline, had significantly better relapse-free survival in ER+/HER2- BC (p=0.034). Pathological examination of TILs after treatment may be a surrogate marker for prognosis in ER+/HER2- BC.

Interaction with the GDF8/11 pathway reveals treatment options for adenocarcinoma of the breast

Breast adenocarcinoma continues to be the most frequently diagnosed tumor entity. Despite established therapy options, mortality for breast cancer remains to be as high as 40,000 patients in the US annually. Thus, a need to develop a patient-oriented, targeted therapy exists. In this study, we investigated the interaction of breast adenocarcinoma with the ubiquitously present protein Follistatin and subsequently the GDF8/11 pathway.We analyzed primary histological samples from adenocarcinoma patients for expression of Follistatin and GDF8/11. Furthermore, expression levels of Follistatin and GDF8/11 in MCF7 were compared with MCF10a cells. From the resulting data, GDF8 and Follistatin were used as chemotherapeutic agents in MCF7 cells and their migratory, proliferative behavior and viability were measured.From the experiments, we were able to detect a significantly increased expression of Follistatin and GDF8/11 in the low malignant breast adenocarcinoma (G1) as compared to benign breast fibroadenoma. Interestingly, a decrease was demonstrated in higher grade malignancies. These findings were accompanied by the clinical observation that increased expression of Follistatin and GDF8 is associated with a higher overall survival rate of breasts cancer patients. Substitution of GDF8 and Follistatin reduces the viability of the MCF7 cells and disrupts the migrative and proliferative potential.In summary, MCF7 cells show high chemosensitivity to Follistatin and especially GDF8 and both proteins might serve as targets to improve systemic treatment in breast cancer. In contrast to most established chemotherapy regimens Follistatin and GDF8 show no cytotoxicity to other organs.

Time to Start Adjuvant Systemic Treatment in Breast Cancer; a Retrospective Cohort Study

Background: According to the World Health Organization (WHO), early diagnosis of cancer was associated with increasing rates of survival for cancers as breast, cervix, mouth, larynx, colon, rectum and skin. Still the optimal time to start adjuvant treatment after definitive surgery is uncertainAim of study: to evaluate the impact of delay to start adjuvant treatment in different biologic subtypes of breast cancer on treatment outcomes as regard response, failure free survival (FFS).Patients and methods: It involved 107 patients with nonmetastatic breast cancer presented to clinical oncology department, Assiut university hospital from January 2011 to December 2012, and were eligible for adjuvant systemic treatment, The time from surgery to the start of 1st cycle of adjuvant systemic treatment was calculated, then this time was divided into three time intervals; ≤30 days, >30 - ≤60 days, and >60 days.Results: 41.1%, 45.8%, 13.1% of patients received adjuvant treatment within 30 days, <30-60 days, and more than 60 days respectively, the median failure free survival was 50±2.104 months (95% CI=45.877-54.125) and was significantly decreased with increasing the time but not significantly differed between different time intervals in the whole study patients, nor in different biologic subtypes except luminal B, patients started early adjuvant treatment, relapsed late with significant effect of different time intervals on the time to relapse, local and distant relapses (P<0.000, P<0.001, P<0.02).Conclusion: Adjuvant systemic treatment for breast cancer should be initiated as early as possible better within 30 days of surgery because of significant poor effect of delay to initiate adjuvant treatment on FFS and TTR.