Adjuvant Chemotherapy For Breast Cancer Research Articles

The use of genomic assays reduces rates of chemotherapy: a single-institution experience.

The National Institute for Clinical Excellence recommends the use of tumour profiling tests to guide adjuvant chemotherapy in breast cancer. The Oncotype DX™ score (Genomic Health) has superseded more traditional tools such as PREDICT in appropriate patients (ER + ve, HER2-ve, lymph node negative and with a Nottingham Prognostic Index [NPI] ≥ 3.4). The aim of this study was to see whether the introduction of Oncotype DX within our institution resulted in an overall reduction in rates of chemotherapy. Data was collected retrospectively using the Somerset Cancer Register, Pathology department databases and the institution's own online medical records system. Two groups were compared: (1) pre-oncotype (Jan 2012-Dec 2014) and (2) post-oncotype (Jan 2016-July 2018). During the pre-oncotype period, 28/82 (34%) patients who would have been eligible for testing (patients who were ER + ve, HER2-ve, and a NPI ≥ 3.4) received chemotherapy compared to 34/135 (25%) who were sent for oncotype during the second study period (p = 0.157). For grade 3 cancers, and those aged under 50, the results were more marked: grade 3 pre-oncotype 23/43 (53%), post-oncotype 29/76 (38%) (p = 0.101), aged under 50 pre-oncotype 8/15 (53%), post-oncotype 10/31 (32%) (p = 0.197). Within our institution, overall rates of chemotherapy have reduced since the introduction of Oncotype DX with the results more marked in subgroups of traditional indicators of tumour aggression. As genomic assays provide a more accurate prediction of the benefit of chemotherapy, its overall reduction has potential cost saving implications as well as reducing risk in patients who will derive little benefit.

Anthracycline-free or short-term regimen as adjuvant chemotherapy for operable breast cancer: A phase III randomized non-inferiority trial

BackgroundDe-escalating anthracycline is gaining popularity for breast cancer patients. We aim to evaluate the non-inferiority of an anthracycline-free or short-term regimen to the standard anthracycline-based regimen for operable patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer. MethodsIt is a prospective, open-label, phase 3, randomized non-inferiority trial from June 1, 2010 to June 1, 2017. Follow-up had been kept until July 2019. This trial was conducted at Fudan University Shanghai Cancer Center. Patients with pT1–3N+ or pT2–3N0 but high-risk (grade II/III, lymphovascular invasion, ≤35 years of age or hormone-receptor negative) HER2-negative operable breast cancer were eligible and stratified by age, pathological tumour stage, pathological node status and hormone-receptor status. Patients were randomized to 6 cycles of docetaxel and cyclophosphamide (TC, n = 524), 3 cycles of cyclophosphamide/epirubicin/fluorouracil followed by 3 cycles of docetaxel (CEF-T, n = 523) or epirubicin and cyclophosphamide for 4 cycles followed by paclitaxel for 12 weeks (EC-P, n = 524) as the intention-to-treat population. Of these patients, 94% completed allocated therapy. Difference in disease-free survival (DFS) compared to EC-P. The prespecified non-inferiority margin was 4.5%, corresponding to the hazard ratio (HR) of 1.44 (one-sided α = 0.05), with an assumed 5-year DFS of 89% for EC-P. FindingsIncluded in the intention-to-treat population were 1571 patients (median [IQR] age, 50 [45–57] years; 92% estrogen receptor [ER]-positive; 59% pN+). Through a median follow-up of 5.5 years, HR for TC versus EC-P was 1.05 (5-year DFS: 85.0% vs. 85.9%; 90% confidence interval [CI]: 0.79–1.39, non-inferior P = 0.048) and for CEF-T versus EC-P, 0.99 (5-year DFS: 85.1% vs. 85.9%; 90% CI: 0.75–1.30, non-inferior P = 0.045). Grade 3 or 4 adverse events for TC included rash (3.9%) and peripheral neuropathy (2.8%) and for CEF-T and EC-P diarrhea and nausea/vomiting were predominant. Results of per-protocol analyses were similar. InterpretationBoth TC and CEF-T are non-inferior adjuvant regimen to EC-P mainly in patients with ER+HER2- breast cancer. TC is a safe regimen that avoids anthracycline-related side effects. FundingThis work was supported by grants from the National Natural Science Foundation of China (Grants 81672600, 81722032, 82072916, and 91959207), the 2018 Shanghai Youth Excellent Academic Leader, the Fudan ZHUOSHI Project, the Municipal Project for Developing Emerging and Frontier Technology in Shanghai Hospitals (grant SHDC12010116), the Cooperation Project of Conquering Major Diseases in the Shanghai Municipality Health System (grant 2013ZYJB0302), the Innovation Team of the Ministry of Education (grant IRT1223), and the Shanghai Key Laboratory of Breast Cancer (grant 12DZ2260100) and the National Cancer Institute (grant P30 CA16058).

61P Estimating the cost of adjuvant chemotherapy in ER+/HER2- early breast cancer and distant recurrence of breast cancer in the UK

Multigene assays (MGAs) can reduce over and under-treatment with adjuvant chemotherapy in oestrogen receptor positive (ER+), human epidermal growth factor 2 negative (HER2-) early breast cancer. The cost of treatment of early breast cancer and distant recurrence of breast cancer are important parameters in the economic evaluation of MGAs. The recent approval of new treatments in the UK, such as CDK4/6 inhibitors, is likely to increase the cost of management of breast cancer. This study aimed to estimate the cost of adjuvant chemotherapy in early breast cancer and the cost of treating distant recurrence in the UK using expert opinion and published sources.

COVID‑19 in a patient receiving adjuvant breast cancer chemotherapy with granulocyte olony‑stimulating factor (G‑CSF) support: A case report

Patients receiving chemotherapy are at high risk for severe infections and complications such as acute respiratory syndrome. The most commonly used adjuvant chemotherapy protocols (docetaxel-cyclophosphamide every 3 weeks or the dose-dense regimen, doxorubicin-cyclophosphamide every 2 weeks followed by paclitaxel) incorporate granulocyte-colony stimulating factor (G-CSF). G-CSF is routinely administered to prevent chemotherapy-associated neutropenia but often results in significant neutrophilia. The present case describes a patient with breast cancer who was successfully treated for severe COVID-19 respiratory syndrome while under adjuvant chemotherapy (docetaxel-cyclophosphamide) treatment and long-term G-CSF support. In addition, the potential effect of G-CSF on the respiratory deterioration of the patient given its cardinal role in innate inflammation and, accordingly, the cytokine storm associated with COVID-19 was described. The case described in the present study indicated how solutions to the immunity challenges faced when treating a patient with chemotherapy may be the source of a larger problem within the coronavirus COVID-19 pandemic.

The effect of comorbidity on primary care use during breast cancer chemotherapy: a population-based retrospective cohort study using CanIMPACT data.

Background:Patients with breast cancer visit their primary care physicians (PCPs) more often during chemotherapy than before diagnosis, but the reasons are unclear. We assessed the association between physical comorbidities and mental health history (MHH) and the change in PCP use during adjuvant breast cancer chemotherapy.Methods:We conducted a population-based, retrospective cohort study using data from the Canadian Team to Improve Community-Based Cancer Care along the Continuum (CanIMPACT) project. Participants were women 18 years of age and older, who had received a diagnosis of stage I–III breast cancer in Ontario between 2007 and 2011 and had received surgery and adjuvant chemotherapy. We used difference-in-difference analysis using negative binomial modelling to quantify the differences in the 6-month rate of PCP visits at baseline (the 24-month period between 6 and 30 months before diagnosis) and during treatment (the 6 months from start of chemotherapy) between physical comorbidity and MHH groups.Results:Among 12 781 participants, the 6-month PCP visit rate increased during chemotherapy (mean 2.3 visits at baseline, 3.4 visits during chemotherapy). Patients with higher physical comorbidity levels or MHH visited their PCPs 4.2 or 1.7 more times, respectively, over 6 months compared to those with low physical comorbidity or no MHH at baseline and 2.5 or 1.1 more times, respectively, over 6 months during treatment. During treatment, the adjusted 6-month rate of PCP visits more than doubled in the group with the fewest physical comorbidities or no MHH compared with baseline (rate ratio 2.52, 95% confidence interval [CI] 2.43–2.61). This increase was lower in those with MHH (rate ratio 1.81, 95% CI 1.68–1.96) and in the highest physical comorbidity group (rate ratio 1.16, 95% CI 1.07–1.28).Interpretation:Patients with breast cancer who have more physical comorbidities and MHH have a higher frequency of PCP visits during adjuvant chemotherapy but lower absolute and relative increases in visits compared with baseline. Therefore, PCPs can expect to see their patients with fewer physical comorbidities and no MHH more often during chemotherapy. Primary care physicians can plan for their patients with high physical comorbidity levels and MHH to continue having frequent appointments while they undergo chemotherapy, and they can expect their patients with low physical comorbidity levels and no MHH to increase the frequency of their visits during chemotherapy, and should be prepared to provide breast cancer–related care to these patients.

An updated review of epidemiology, risk factors, and management of male breast cancer.

Unlike female breast cancer, male breast cancer (MBC) is rare and not very well understood. Prospective data in the management of MBC are lacking and majority of treatment strategies are adopted from the established guidelines for breast cancer in women. The understanding of biology, clinical presentation, genetics, and management of MBC is evolving but there still remains a large knowledge gap due to the rarity of this disease. Older age, high estradiol levels, klinefelter syndrome, radiation exposure, gynecomastia, family history of breast cancer, BRCA2 and BRCA1 mutation are some of the known risk factors for MBC. Routine screening mammography is not recommended for asymptomatic men. Diagnostic mammogram with or without ultrasound should be considered if there is a suspicion for breast mass. Majority of men with early-stage breast cancer undergo mastectomy whereas breast conserving surgery(BCS) with sentinel lymph node biopsy (SLNB) remains an alternative option in selected cases. Since the majority of MBC are hormone receptor positive (HR+), adjuvant hormonal therapy is required. Tamoxifen for a total of 5 to 10years is the mainstay adjuvant hormonal therapy. The role of neoadjuvant and adjuvant chemotherapy for early-stage breast cancer is uncertain and not commonly used. The role of gene recurrence scores like oncotype Dx and mammaprint is evolving and can be used as an aid for adjuvant chemotherapy. Majority of metastatic MBC are treated with hormonal therapy with either tamoxifen, gonadotropin-releasing hormone agonist (GnRH) with aromatase inhibitors (AI), or fulvestrant. Chemotherapy is reserved for patients with visceral crisis or rapidly growing tumors.

P038 - Scenarios of cost-savings associated with Oncotype DX® test-guided decisions for adjuvant chemotherapy in early breast cancer in Germany

P038 - Scenarios of cost-savings associated with Oncotype DX® test-guided decisions for adjuvant chemotherapy in early breast cancer in Germany

Adjuvant chemotherapy and survival outcome in node-negative breast cancer with a 21-gene recurrence score of 26-30.

Aim: To investigate thebenefit of chemotherapy among early-stage breast cancer patients with 21-gene recurrence scoresof 26-30. Methods: We identified 3754 patients in the Surveillance, Epidemiology, and End Results database. Results: 57.6% of the patientsreceived adjuvant chemotherapy. Patients with higher tumor grade, larger tumorsand younger age were more likely to receive chemotherapy. The receipt of chemotherapy was independently associated with better breast cancer-specific survival than in patientswithout chemotherapy before (p = 0.016) and after (p = 0.043) propensity score matching. The sensitivity analyses showed that survival gain was pronounced in patients with poorly differentiated orundifferentiated disease. Conclusions: Adjuvant chemotherapy improves the outcome for early-stage breast cancer with 21-gene recurrence score of 26-30, especially for patients with high-grade tumors.

Improving early breast cancer treatment: the role of granulocyte colony-stimulating factor

Breast cancer is still the leading cause of death in patients with malignant tumors. Among women with breast cancer, standard combination chemotherapy with anthracyclines and taxanes reduces mortality from this disease by about one third compared to patients not receiving chemotherapy and is the standard for neoadjuvant or adjuvant chemotherapy of breast cancer. Understanding the patterns of tumor growth has made it possible to improve the current paradigms of the treatment of early forms of breast cancer and to use dose-dense chemotherapy regimens to achieve better treatment results. Nowadays, chemotherapy in a dose-dense regimen for breast cancer is the preferred option in all world and Russian clinical guidelines. However, the use of such chemotherapy regimens significantly increases the incidence of side effects, primarily febrile neutropenia. The appearance of more effective methods of supportive care, particularly short-acting and long-acting granulocyte colony-stimulating factor, in clinical practice has made it possible to use dose-dense chemotherapy regimens to increase the effectiveness of the treatment.

Abstract PD12-01: Evaluation of sleep problems and their association with febrile neutropenia, leucopenia and infections in women receiving adjuvant chemotherapy for breast cancer in the Canadian Cancer Trials Group MA.21 trial

Abstract BackgroundInsomnia is a frequent complaint in patients with cancer. Sleep problems can affect immune functioning in healthy individuals. Our aim was to evaluate the association between sleep disturbance and the risk of febrile neutropenia, leukopenia and infections in patients treated with chemotherapy in an adjuvant setting for breast cancer.MethodologyThis is a retrospective study using the Canadian Cancer Trial Group data collected for the MA.21 trial, in which three adjuvant chemotherapy regimens (CEF, EC-T dose dense or AC-T) were compared in 2104 patients with node positive or high-risk node negative breast cancer. A total of 1731 patients had completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) and 1727 patients had completed the Breast Cancer Chemotherapy Questionnaire (BCQ) quality of life questionnaires, which both include a question about sleep difficulties. The primary definition for patients with insomnia was a score of three (quite a bit) or greater at Question 11 (Have you had trouble sleeping? with answers ranging from one (not at all) to four (very much)) on the EORTC QLQ-C30 questionnaire. We compared patients classified as having “clinical insomnia” based on their response to this question with patients considered “good sleepers”. The primary endpoint was the risk of febrile neutropenia. Secondary endpoints were the risks of grade one or more leukopenia, neutropenia and infection. ResultsFebrile neutropenia was more frequent in patients with sleep problems compared with those without, with 16.3% and 12.2% of patients having at least one episode in each group respectively (p value = 0.01 in the univariate analysis (table 1)). However, after adjustment for potential confounders in the multi-variate analysis, it was not statistically significant with an odds ratio of 1.07, a 95% confidence interval of 0.76-1.50 and a p value of 0.71. Similarly, no statistically significant difference in the risk of leukopenia could be demonstrated in the multi-variate analysis for patients with sleep problems with an odds ratio of 0.92 a 95% confidence interval of 0.69-1.24 and a p value of 0.59. No significant association could be found between sleep problems and neutropenia and infections. In an unplanned exploratory analysis, chemotherapy dose reductions were significantly more frequent in patients with sleep problems with 30.6% in this group compared to 21.8% in good sleepers, with a p value <0.0001. ConclusionWhile our univariate analysis suggested an increased risk of febrile neutropenia and leucopenia in patients with sleep problems, after adjustment for confounders, we could not show a statistically significant association in women undergoing adjuvant chemotherapy for high-risk locoregional breast cancer. Table 1: Univariate analysis of primary and secondary outcomes in patients with sleep problems and good sleepersCharacteristicsSleep problem= yesSleep problem = noFebrile neutropeniaNo781 (83.7%)701 (87.8%)Yes152 (16.3%)97 (12.2%)P-value0.01White blood cell count (WBC)Grade 0157 (16.8%)141 (17.7%)Grade 1135 (14.5%)138 (17.3%)Grade 2184 (19.7%)186 (23.3%)Grade 3214 (22.9%)173 (21.7%)Grade 4243 (26.1%)160 (20.1%)P-value0.02NeutropeniaGrade 0778 (83.4%)700 (87.7%)Grade 10 (0%)1 (0.1%)Grade 22 (0.2%)0 (0%)Grade 3152 (16.3%)96 (12.0%)Grade 41 (0.1%)1 (0.1%)P-value0.014InfectionGrade 0619 (66.4%)564 (70.7%)Grade 168 (7.3%)62 (7.8%)Grade 2158 (16.9%)110 (13.8%)Grade 387 (9.3%)61 (7.6%)Grade 41 (0.1%)1 (0.1%)P-value0.24Chemotherapy delayNo1 (0.1%)12 (1.5%)Yes932 (99.9%)786 (98.5%)P-value0.0008Chemotherapy dose reductionNo648 (69.4%)624 (78.2%)Yes285 (30.6%)174 (21.8%)P-value< 0.0001 Citation Format: Audreylie Lemelin, Josée Savard, Michelle Chen, Margot Burnell, Mark N Levine, Lois Shepherd, Bingshu E Chen, Julie Lemieux. Evaluation of sleep problems and their association with febrile neutropenia, leucopenia and infections in women receiving adjuvant chemotherapy for breast cancer in the Canadian Cancer Trials Group MA.21 trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD12-01.

Abstract PS13-04: Impact of delayed initiation of adjuvant chemotherapy in early breast cancer: Analysis from Taiwan National breast cancer registry database

Abstract Background:In 2017, there are more than 14,000 cases of newly diagnosed breast cancer in Taiwan. With the popularity of early screening policy and social-awareness, the proportion of early breast cancer has increased significantly in the last decades. For the high risk group with early breast cancer, adjuvant systemic chemotherapy could provide lower breast cancer recurrence rate and better overall survival rate. In Taiwan, every citizen must join the National Health Insurance (NIH), and the NIH would cover the whole expanse of adjuvant chemotherapy. Theoretically, all breast cancer patients could receive their condign chemotherapy regardless of their social economic status. The optimal initiation timing of adjuvant chemotherapy is undiscovered, and the effect of delay initiation is still under contestation. In this study, we try to identify the relationship between initiation time of chemotherapy and survival outcome, and different breast cancer subtypes would be analyzed separately. We also evaluate many associated factors that may delay chemotherapy initiation or survival status.Material and Methods:In this observational, populational-based study using Taiwan national breast cancer registry database, we studied 110,784 patients diagnosed with Stage I~III breast cancer between January 1, 2006 and Deccember 31, 2016. Time to chemotherapy(TCC) was defined as the days between surgery and the initial dose of adjuvant chemotherapy. We categorized patients into initiate chemotherapy within 30 days, 31~60 days, 61~90 days, and more than 91 days. The patient demography, tumor biology, lymph node status, type of breast surgery, receiving reconstructive surgery or not, radiation therapy, immunohistochemistry data (estrogen receptor, progesterone receptor, and human epidermal growth factor 2[HER2]), and we categorized patients according to different breast cancer subtypes. Univariate analysis with Kaplan-Meier method is used to evaluate TTC influence, and log-rank test is used to compare differences between groups. Multivariate logistic regression model is used to identify important factors associated with delayed chemotherapy initiation and survival.Preliminary Results:Totally 72840 patients were enrolled in this study, and the median age at initial diagnosis was 52.4 years old. Delayed wound healing and breast reconstruction are the main factors associated with delated TTC. Comparing with TTC<30 days group, TTC of 31~60 days group showed no difference in disease-free survival and overall survival, while TTC of 61~91 days group had a trend of lower disease-free survival (p=0.12). TTC more than 91 days had worse disease-free survival (HR=1.16, 95%CI=1.03~1.38) and overall survival (HR=1.23, 95%CI=1.08~1.52). We assumed initiate first chemotherapy more than 90 days as delated TTC as generally accepted in previous publications. In subgroup analysis, delayed TTC caused worse disease-free survival especially in triple negative group (HR=1.42, 95%CI=1.21~1.68) and HER2 group (HR=1.38, 95%CI=1.22~1.55).Conclusion:For breast cancer patients who assumed to receive adjuvant systemic chemotherapy, delayed in initiation of chemotherapy (more than 90 days) may result in worse outcome, especially in triple negative breast cancer and HER2 group. Besides the above preliminary result, other multivariate analysis and intergroup comparison are still ongoing. More information will reveal in SABCS 2020. Citation Format: Junping Shiau, Fang-Ming Chen, Ming-Feng Hou. Impact of delayed initiation of adjuvant chemotherapy in early breast cancer: Analysis from Taiwan National breast cancer registry database [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-04.

Abstract PS9-27: Estimation of clinical benefit and economic burden for using a commercial 70-gene signature test for Brazilian breast cancer patients in the public health system

Abstract Background The clinical benefit of adjuvant chemotherapy (CT) for breast cancer (BC) depends on several factors, like menopausal status, stage and molecular subtype. Commercial available gene signatures make possible a more accurate selection of the patients who could benefit more with adjuvant chemotherapy. In Brazil, gene signatures are not available to public health system users, nor even reimbursed for privately insured patients, making this matter a major cause of frustration for patients and oncologists. MINDACT trial evaluated 70-gene signature MammaPrint (70-GS) as predictive test for chemotherapy benefit. Long-term follow up showed premenopausal patients who had not received CT and were in in the high clinical risk/ low genomic risk group presented unfavorable outcomes. We aimed to estimate clinical impact and economic burden that a hypothetical access to 70-GS may result based on a Brazilian BC population treated in a university hospital. Methods Medical records from BC patients who received neo/adjuvant chemotherapy from January/2018 to June/2020 at the Hospital das Clínicas de Ribeirão Preto - USP (HCRP-USP) were retrospectively analyzed. The following inclusion criteria were considered to select patients who could benefit most with 70-GS: stage I or II invasive BC, tumors smaller than 5 cm, up to three positive lymph nodes (LN+), postmenopausal status and HR+/HER2- (hormone receptor-positive, HER2-negative) tumors. Online search for costs and reimbursed values. The Brazilian public health system reimburses clinics R$ 571 (US$ 107) (US$ 1=R$ 5.32; July 1, 2020) each month a patient receives adjuvant CT for stage I BC and R$ 800 (US$ 150) each month for stage II BC. The 70-GS test, purchased privately, costs R$ 15,000 (US$ 2,820). The study was approved by the local ethics committee (HCFMRPUSP no 4.078.614). Results From Jan/2018 to June/2020, 311 patients were treated with neo/adjuvant chemotherapy. Mainly 4 cycles of AC (doxorubicin-cyclophosphamide), 8 cycles of ACT (AC + docetaxel or paclitaxel) or 4 cycles of TC (docetaxel-cyclophosphamide) regimens were delivered, which lasted from 3 to 6 months. For an entire CT period, we estimate the maximum reimbursement amount of R$ 4,800 (US$ 752) (6 months for stage II BC). In our population, patient who received CT, according to subtypes, were 174 (56%) HR+/HER2-, 30 (10%) HR+/HER2+, 38 (12%) HR-/HER2+ and 69 (22%) triple-negative. Among RH+/HER2-, 96 (55%) were postmenopausal BC, 77 (44%) were premenopausal BC and one was male BC (1%). Taking in accountpostmenopausal stage I and II BC, tumors <5 cm and ≤3 LN+, a total of 54 patients who received CT (17%) would be candidates to 70-GS testing. For this group, the maximum reimbursement with CT would be R$ 259,200 (US$ 48,722) while the costs with 70-GS would be R$ 810,000 (US$ 152,280). Conclusions Among 311 patients who received CT at our institution, 54 met the inclusion criteria we chose as the most beneficial to perform 70-GS test. Considering that MINDACT trial found that 46% of high clinical risk may not require CT, approximately 25 patients (8%) could have avoided CT, saving R$ 120,000 (USS$ 22,556). The 70-GS test valuation for the public health system, considering only savings from chemotherapy, would be R$ 2,222 (US$ 418) and the current cost of 70-GS is 6.75 times higher than the money saved. Additional pharmacoeconomic analyses should include the estimated costs of early and late toxicities (i.e. febrile neutropenia, leukemia and cardiotoxicity) for this population, which can reduce the difference between the cost of 70-GS test and the amount saved. A national agreement between the company and the government could also contribute to increase access and make treatment de-escalation a reality also in lower-middle-income countries. Citation Format: Franklin F Pimentel, Isabela PC Buzatto, Tamara CGF Rodrigues, Jessica MC Borba, Karoline PI Peruchi, Jurandyr M de Andrade, Daniel G Tiezzi. Estimation of clinical benefit and economic burden for using a commercial 70-gene signature test for Brazilian breast cancer patients in the public health system [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-27.

Abstract PS6-51: Identification of a low-risk luminal breast cancer cohort that may not benefit from multi-gene testing

Abstract Purpose: Dutch clinical risk criteria (low-risk definition: age > 35 years and (grade 1 with tumor ≤3cm, grade 2 with tumor ≤2cm, or grade 3 with tumor ≤1cm) have been used to stratify the benefit of MammaPrint and Oncotype DX for the decision-making regarding adjuvant chemotherapy for early-stage luminal breast cancer. We propose that the criteria could help to identify low-risk patients who could barely benefit from multi-gene testing. Materials and methods: Breast cancer patients from Taiwan Cancer Database initially treated with primary surgeries between 2008 and 2012 who met the following criteria: (1) pathologic node-negative, (2) hormone receptor-positive, (3) HER2-negative, (4) undergone hormonal therapy, and (5) a minimum follow-up time of 5-year if free from any event, were enrolled in this study. Out of the total 2679 eligible patients, 1074 (40.1%) patients received adjuvant chemotherapy in addition to endocrine therapy. The study endpoints included breast cancer-specific survival (BCSS) and overall survival (OS). Kaplan-Meier statistics estimated the difference between clinical outcomes in low- and high-risk groups. Results: The median follow-up time of BSCC and OS was 5.9 years (range, 0-7 years) and 5.8 years (range, 0-7 years), respectively. There were statistical significances of 5-year BCSS (n=2679) and 5-year OS (n=2636) between low-risk and high-risk groups (in both endpoints, P < 0.0001). According to the Dutch criteria, low-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 99.0% vs. 99.2% and a 5-year OS of 98.4% vs. 97.4%, respectively. High-risk patients with and without adjuvant chemotherapy had a 5-year BCSS of 97.7% vs. 98.1% and a 5-year OS of 96.4% vs. 95.3%, respectively. Conclusion: The benefit of chemotherapy in low-risk patients classified by Dutch criteria might be very small since the breast cancer mortality was less than 1% with a minimum of 5-year follow-up. Dutch criteria cannot identify high-risk patients who would benefit from chemotherapy. We assumed that multi-gene testing in low-risk patients would not be cost-effective. Citation Format: Lei Lei, Han-Ching Chan, Tzu-Pin Lu, Xian-Yuan Miao, Zi-Yan Yang, Jia-Huan Huang, Xiao-Jia Wang, Hung-Chun Skye Cheng. Identification of a low-risk luminal breast cancer cohort that may not benefit from multi-gene testing [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-51.

Abstract PS13-05: A phase 2 study of oral paclitaxel and encequidar (oPac+E) in the treatment of cutnaeous angiosarcoma: The breast angiosarcoma subgroup

Abstract Background Cutaneous angiosarcomas are highly aggressive malignant tumors with poor prognosis. Currently there is no FDA-approved treatment. oPac+E is a combination of oral paclitaxel and a novel oral P-glycoprotein inhibitor, Encequidar. Materials and Methods: This is a phase-2 study evaluating the activity, safety and tolerability of oPac 205mg/m2 + E 12.9 mg once daily for 3 consecutive days weekly for patients with unresectable cutaneous angiosarcoma. Tumour response was evaluated every 6 weeks using RECIST and photography. Results: From Aug-2018 to May-2020, 7 of 26 enrolled patients (pts) had breast cutaneous angiosarcoma. All had previous breast cancer, mastectomy and radiotherapy and/or adjuvant chemotherapy, no prior taxane for angiosacoma and no metastatic disease. Median age was 66 yrs (range 49-76). Best objective response rates were: complete response (CR) 43% (3/7 pts), partial response (PR) 14% (1/7 pts), stable disease (SD) 43% (3/7 pts), progressive disease (PD) 0%. Furthermore, 3 pts (43%) who had inoperable lesions were deemed operable after Oraxol treatment and received curative intent surgical resection. Median progression free survival (PFS) was 17 weeks. oPac+E was generally well tolerated. Grade-3 treatment related adverse events (AEs) occurred in 5 pts: diarrhea=1, fatigue=2, neutropenia =1, dyspnea=1, dehydration=1, pneumonitis=1. Grade-4 AE were neutropenia in 2 pts. Grade-2 paraesthesia=1. All pts fully recovered. Dose reductions were needed in 3 subjects. No patients discontinued treatment due to AEs. To date no patients died. Conclusions: oPac+E may provide an effective oral treatment for radiation-associated breast angiosarcoma, with a high clinical benefit rate (CR + PR+ SD=100%), durable response and enabled resection of unresectable tumors. It is generally well tolerated even in elderly patients; with low incidence of neuropathy. It may allow patients to avoid hospital IV chemotherapy visits and the option of home treatment. Citation Format: Vinod Ravi, Michael Wagner, Tom Wei-Wu Chen, Herbert H Loong, Robert Mennel, Cheuh-Chuan Yen, Glen Clack, David Cutler, Rudolf Kwan, Wing=Kai CHan. A phase 2 study of oral paclitaxel and encequidar (oPac+E) in the treatment of cutnaeous angiosarcoma: The breast angiosarcoma subgroup [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-05.

Associated factors and outcomes of delaying adjuvant chemotherapy in breast cancer by biologic subtypes: a National Cancer Database study.

PurposeSeveral studies have evaluated the role of delayed initiation of adjuvant chemotherapy (AC) in breast cancer (BC), but the results have remained controversial and an optimal time has not been defined. Our aim was to determine the effect of time to starting AC from the date of surgery on survival of BC patients, based on estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, using data from the National Cancer Database (NCDB).MethodsA total of 332,927 Stage I–III BC patients who received AC from 2010 to 2016 were analyzed. We included all ER, PR and HER2 statuses and excluded patients with stage 4 and stage 0 (DCIS) disease. The cohort was divided into five groups based on the time of initiating AC from the date of the most definitive surgery i.e., ≤ 30 days, 31–60 days, 61–90 days, 91–120 days and > 120 days. They were further divided into five subgroups based on the receptor status.ResultsHazard ratio (HR) estimates and Kaplan–Meier (KM) analysis shows that starting AC by 31–60 days shows the best survival outcome in all the subtypes, except in hormone positive/HER2 negative BC in which 31–60 days and 61–90 days have similar outcomes.ConclusionsAfter surgery for BC, it takes around 4–6 weeks to begin AC and delay in initiating the same leads to poor outcomes. Our results are particularly significant in triple-negative breast cancer (TNBC), similar to prior studies showing a benefit to starting AC as early as possible after surgery.

The role of capecitabine-based neoadjuvant and adjuvant chemotherapy in early-stage triple-negative breast cancer: a systematic review and meta-analysis

BackgroundThe role of capecitabine in neoadjuvant and adjuvant chemotherapy for early-stage triple-negative breast cancer (TNBC) is highly controversial. Our meta-analysis was designed to further elucidate the effects of capecitabine on survival in early-stage TNBC patients and its safety.MethodsPubMed, Embase, and papers presented at several main conferences were searched up to December 19, 2019, to investigate capecitabine-based versus capecitabine-free neoadjuvant and adjuvant chemotherapy in TNBC patients. Heterogeneity was assessed using I2 test, combined with hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) computed for disease-free survival (DFS), overall survival (OS), and over grade 3 adverse events (AEs).ResultsA total of 9 randomized clinical trials and 3842 TNBC patients were included. Overall, the combined capecitabine regimens in neoadjuvant and adjuvant chemotherapy showed significantly improved DFS (HR = 0.75; 95% CI, 0.65–0.86; P < 0.001) and OS (HR = 0.63; 95% CI, 0.53–0.77; P < 0.001). In subgroup analysis, there were improvements in DFS in the groups with addition of capecitabine (HR = 0.64; 95% CI, 0.53–0.78; P < 0.001), adjuvant chemotherapy (HR = 0.73; 95% CI, 0.63–0.85; P < 0.001), and lymph node positivity (HR = 0.62; 95% CI, 0.44–0.86; P = 0.005). Capecitabine regimens were related to higher risks of diarrhea (OR = 2.88, 95% CI 2.23–3.74, P < 0.001), stomatitis (OR = 2.01, 95% CI 1.53–2.64, P < 0.001) and hand–foot syndrome (OR = 8.67, 95% CI 6.70–11.22, P < 0.001).ConclusionThis meta-analysis showed that neoadjuvant and adjuvant chemotherapy combined with capecitabine significantly improved both DFS and OS in early-stage TNBC patients with tolerable AEs. There were benefits to DFS in the groups with the addition of capecitabine, adjuvant chemotherapy, and lymph node positivity.

Myosteatosis evaluation using erector spinae and psoas muscles to predict adverse events during adjuvant chemotherapy for breast cancer.

Myosteatosis (intramuscular adiposity) is predictive of chemotherapy toxicity in women undergoing adjuvant chemotherapy for breast cancer (BC). We evaluated a novel, user-friendly and cost-effective technique utilizing a Picture Archiving and Communication Systems (PACS) tool that is readily available in the electronic medical record (EMR), using skeletal muscle density (SMD) to detect myosteatosis and then compared PACS results with those derived from widely used body composition software (SliceOMatic, QC, Canada). Using retrospective data from a sample of women with early BC (Stage I-III) who had CT scan and received chemotherapy. Pearson correlation coefficients were used to compare SliceOMatic with PACS results. Associations of PACS results with chemotherapy-related adverse events were evaluated using multivariable (MV) log-binomial models adjusted for age, race, BMI, anthracycline-based therapy, and number of comorbidities. In 338 patients, mean age was 51, 32% were non-white, and 40% had obesity (BMI ≥ 30kg/m2). Correlation of SMD using SliceOMatic whole muscle measurements with PACS psoas muscle was 0.76 (p < .0001) and with PACS erector spinae muscle 0.91 (p < .0001). Using PACS psoas muscle, myosteatosis was associated with any adverse event [RR 1.66, CI 1.22-2.26 (p < .0001)], dose reduction [RR 1.63, CI 1.01-2.65 (p = .05)], and early treatment discontinuation [RR 2.14, CI 1.10-4.14 (p = 0.03)]. Using PACS erector spinae muscle, myosteatosis was associated any adverse event [RR 1.59, CI 1.11-2.27 (p = 0.01)] and dose reduction [RR 1.91, CI 1.07-3.42 (p = .03)]. Skeletal muscle density measures using PACS correlated strongly with SliceOMatic results and both are similarly predictive of chemotherapy-related adverse events.

Vibration Perception Threshold and Heart Rate Variability as methods to assess chemotherapy-induced neuropathy in women with breast cancer – a pilot study

PurposeChemotherapy-induced peripheral neuropathy (CIPN) is a recognized adverse effect of standard (neo)adjuvant chemotherapy in breast cancer (BC) treatment. However, there is no consensus on a validated method for assessing CIPN. Heart rate variability (HRV) and vibration perception threshold (VPT) could be used as objective measures to describe CIPN. The aim of this pilot study was to investigate whether subjectively reported CIPN was associated with altered HRV and VPT in BC patients. MethodsWe performed a cross-sectional pilot study evaluating 30 BCE patients previously treated with chemotherapy, 26 BCE patients who did not receive chemotherapy, and 22 controls without breast cancer. Self-reported CIPN was registered for the BC patients. All participants were subjected to multi-frequency vibration analyses to determine VPT along with short ECG measurements to determine HRV measures. ResultsSelf-reported CIPN was registered in 14 (46.6%) BC patients treated with chemotherapy. The VPT at 64 Hz (P = 0.022) and mean HR (P = 0.022) were significantly higher and the HRV measures SDNN (P = 0.023), RMSSD (P = 0.007), LF (P = 0.050) and HF (P = 0.045) were significantly lower in BC patients reporting CIPN compared to controls when adjusted for age. VPT at 64 Hz and 125 Hz were significantly higher in BC patients not reporting CIPN compared to controls when adjusted for age. ConclusionWe found elevated VPT and mean HR along with decreased HRV parameters in 14 BCE patients reporting CIPN. These findings support the need for further investigation into whether HRV and vibration analysis could contribute to an objective assessment of CIPN.

A nanoparticle-containing polycaprolactone implant for combating post-resection breast cancer recurrence.

The recurrence and metastasis of tumor after surgery is the main cause of death for patients with breast cancer. Systemic chemotherapy suffered from low delivery efficiency to tumors and the side effects of chemo drugs. Localized chemotherapy using drug-containing implants is an alternative, while the reconstruction of breast tissue is generally considered after chemotherapy, resulting in a second surgery for patients. Here, we describe a strategy using implantable drug-containing polymeric scaffolds to deliver chemo drugs directly to the post-resection site, and simultaneously provide mechanical support and regenerative niche for breast tissue reconstruction. When doxorubicin was loaded in mesoporous silica nanoparticles and subsequently incorporated into polycaprolactone scaffolds (DMSN@PCL), a 9-week sustained drug release was achieved post implantation in mice. The local recurrence of residual tumor after surgery was significantly inhibited within 4 weeks in a post-surgical mouse model bearing xenograft MDA-MB-231 tumor. DMSN@PCL scaffolds exhibited good biocompatibility in mice during the treatment. We believe our strategy holds great promise as an adjuvant localized chemotherapy in clinics for combating post-resection breast cancer recurrence.

PROGNOSTIC VALUE OF TOPOISOMERASE 2-ALPHA AND B-MYB IN EARLY BREAST CANCER TREATED WITH ADJUVANT CHEMOTHERAPY.

SUMMARYBreast cancer is the most common malignancy in females. Despite its well-established prognostic factors, our prognostic ability at an individual patient level remains limited. In this study, the immunohistochemical expression of B-Myb and DNA topoisomerase 2-alpha (Topo2a) was analyzed in primary tumors to identify patients with a higher risk of disease recurrence after adjuvant chemotherapy for early invasive breast cancer. We analyzed a cohort of 215 early invasive breast cancer patients having undergone surgery from 2002 to 2003 at the Zagreb University Hospital Centre, including 153 patients treated with adjuvant chemotherapy. All of them were followed-up prospectively for at least ten years according to routine institutional practice. Statistically significant correlations were found between B-Myb and Topo2a expression levels and particular well-established prognostic factors. B-Myb expression was lower in estrogen receptor (ER)-positive tumors (p=0.0773), whereas larger tumors and those with positive lymphovascular invasion displayed a statistically significantly higher B-Myb expression (p=0.0409 and p=0.0196). Higher tumor grade indicated higher Topo2a values (p=0.0102 and p=0.0069). The subgroup with the expression of both proteins above the median value had an almost statistically significantly (p=0.0613) inferior prognosis compared to the rest of the cohort. Study results showed the B-Myb and Topo2a expression to have a prognostic value in breast cancer patients after adjuvant chemotherapy, which should be additionally explored in future studies in a larger patient cohort.