No abstract

INTRODUCTION Neoadjuvant chemotherapy (NAC) is increasingly utilized in the treatment of Breast Cancer to downsize the tumour, improve surgical outcome and to achieve a complete pathological response (pCR). Current regimes result in response rates of 40-80% depending on the subtype of the tumour and the presence of pCR, noted in 13-26% patients, is considered an indicator of excellent prognosis. An additional advantage of NAC is the assessment of the in vivo chemo-responsiveness of the tumor.FDG-PET/CT (fluorodeoxyglucose positron emission tomography/computed tomography) provides morphologic as well as functional imaging. Preliminary studies suggest it provides a more accurate evaluation of tumour response compared to other techniques. Moreover, studies suggest its utility in identifying non-responders early during NAC so as to enable a switch to an alternate more effective regimen, thereby preventing avoidable toxicity associated with an ineffective drug regimen.In this study, we evaluated metabolic changes on FDG-PET after 2 cycles of NAC to predict pathological response to NAC. PATIENTS AND METHODS A prospective cohort of patients with newly diagnosed, non-metastatic, T1-4, N1-2/3 breast cancer, undergoing NAC from October 2012 to December 2019 at a tertiary referral center, were entered in this study. The tumor size was assessed by the same surgeon at baseline and after every cycle of NAC. FDG-PET/CT was performed before commencement of NAC (PET1) and after the 2nd cycle of NAC (PET2) and the early metabolic response (ΔSUV max i.e. change in maximum standardized uptake value) was determined. All patients underwent surgery on completion of NAC and the pathological response following surgery served as the reference standard for the evaluation of the therapy response on FDG-PET/CT. Patients were classified into Responders [pCR and Minimal Residual Disease (MRD)] and Non-responders [Gross Residual Disease (GRD)] as per the classification of Honkoop et al. Receiver operating characteristic analysis was performed to identify an optimal threshold value of reduction rate (RR) of maximum standardized uptake values (ΔSUVmax) to accurately predict pathological response. RESULTS Out of 135 patients, 4 patients had bilateral cancer, resulting in 139 breast lesions assessed at baseline by FDG PET CT of which 51.07% were Luminal, 21.58% HER2 + and 27.34% TNBC. The mean age was 49 years (range 27-72), 54.81% were premenopausal, 45.19% post-menopausal, 85 (61.15%) were stage II cancers and 54 (38.84%) had stage III cancers. The overall pCR rate was 24.46%, 65 (46.76%) were Responders (pCR+MRD) and 74 (53.23%) Non-responders (GRD). The mean PET1 SUVmax of the tumors in Responder group was 14.5 and of Non-responder group was 9.4. The mean PET2 SUVmax for Responders was 4.28 and Non-responders was 7.52. The RR after the second course of NAC (ΔSUV), was significantly higher for Responders, 62.38% (+24.79) as compared to Non-responders 25.81% (+57.57), (p <0.0001). The optimal ΔSUV threshold to discriminate between Responders and Non-responders was 51% (69.35% sensitivity; 69.12% specificity) with area under the curve being 0.744. The negative predictive value for histopathologic Non-responders was 71.2 (CI 62.2- 78.8). CONCLUSIONS Metabolic change in FDG/PET-CT after 2 cycles of NAC can predict pathological response and, a ΔSUVmax of more than 51%, can differentiate Responders from Non- responders. Early determination of Non-responders could help identify a group which may benefit from an early change to an alternate regimen. Citation Format: Vinay Deshmane, Anuja Raniwala, Abhiyutthan Singh, Sachin Almel, Natasha Singh, Anita Bhaduri, Raj Jatale. The utility of PET-CT after the second cycle of neoadjuvant chemotherapy for monitoring early metabolic change to predict pathologic response [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 PS13-43.

INTRODUCTION Early breast cancer (EBC) which is hormone receptor positive, HER2 negative and 0-3 Lymph node positive, defines a Luminal subtype with an excellent outcome and the benefit of adjuvant chemotherapy in this subgroup of patients is increasingly questioned. Gene-expression profile tests have evolved to help stratify risk and to individualise treatment decisions. The 21-gene recurrence-score assay, “Oncotype DX” (ODX) is a genomic test used to quantify the likelihood of distant recurrence (Recurrence Score i.e. RS) and predict chemotherapy benefit. Although it is included in international guidelines as a tool to identify patients who could safely avoid adjuvant chemotherapy, its utility is restricted due to cost in countries with limited resources where it is not covered by insurance. The “NHS Predict” (NHSP) is a freely available online prognostic and predictive test based on cancer registry data. It utilises an algorithm based on clinical parameters and biomarker status to provide an estimate of survival as well as the potential benefit of third generation chemotherapy, hormonal and targeted therapy. The NHSP is based on “Clinical Risk (CR)” while the ODX is based on “Genomic Risk (GR)” assessment. The present study was undertaken to compare the results obtained by ODX with those obtained by NHSP so as to determine the concordance of the two tests and establish the utility of the NHSP in resource-constrained countries. PATIENTS AND METHODS Patients with early ER positive, HER2 negative, 0-3 nodes positive breast cancer, who underwent the ODX assay from January 2010 to March 2020 at a tertiary referral centre were entered into this study. Patients were stratified as per the ODX RS into Low (RS= 0-20 for ≤ 50 years, 0-25 for >50 years) and High (RS= >21 for ≤ 50 years and 26-100 for >50 years) risk for recurrence with absolute chemotherapy benefit (ACB) estimated to be ≤7% and >7% respectively at 9 years.Subsequently, the NHS Predict 2.2 tool (https://breast.predict.nhs.uk/tool ) was used to compute the absolute benefit of third generation chemotherapy for each of these patients. Relevant clinical data i.e. age, menopausal status, tumour size, grade, Ki-67, ER/PR/HER2 status, nodal status and method of detection was entered into the algorithm. The ACB at 10 years, as determined by NHSP, was stratified into Low risk≤ 7% and High risk >7% so as to correspond to the ACB derived from ODX. The results obtained by NHSP were compared to those of the ODX to determine the concordance between the two tests. RESULTS 104 patients were entered into the study. The mean age was 53 years (range 31-76 years), 39.4% were premenopausal and 60.5% post-menopausal. The average tumour size was 19.4mm (range 8-55mm) with 61.53% T1, 36.53% T2 and 1.92% with T3 disease.14.4% were grade 1, 66.3% grade 2, and 19.2% grade 3. 74% were lymph node negative and 14.4%, 9.6% and 0.96% had 1, 2 and 3 positive nodes respectively. On ODX evaluation, low RS was seen in 87 (83.65%), and high RS in 17(16.34%) patients. As per NHSP, 99 (95.19%) patients were classified into low CR and 5 (4.8%) into high CR. There was 82.7% (86/104) concordance between NHSP and ODX with discordance in 18 patients. Of the concordant group, 84 had low CR and GR and 2 had high CR and GR. In the discordant group 15 patients had low CR on NHSP but high GR on ODX and while 3 patients had a high CR on NHSP but ODX showed low GR. CONCLUSIONS In a group of patients with low clinical risk EBC there is high concordance between the NHSP and ODX tests. There is a subgroup of patients with discordant results in whom the ODX may identify patients who could potentially benefit with adjuvant chemotherapy. NHSP can aid decision making regarding adjuvant chemotherapy and identify patients who could potentially avoid chemotherapy in low risk early breast cancer. Citation Format: Vinay Deshmane, Anuja Raniwala. A comparison of oncotype DX and NHS predict to assess the benefit of adjuvant chemotherapy in patients with early breast cancer [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 PS6-38.

INTRODUCTION Oncoplastic breast surgery (OPS), has widened the scope of breast conserving surgery (BCS) enabling larger resections with acceptable oncological safety and cosmetic outcomes. It often involves longer incisions and additional contralateral symmetrization procedures on the normal breast. However, patient’s perceptions on outcome may differ from that of the clinician and it is essential to evaluate feedback from patients undergoing OPS to determine the acceptability of these complex procedures in clinical practice. In this regard Health-related quality of life measures (HR-QoL) are an excellent means of evaluating the outcome of medical care. Further, it is well known that socio-cultural differences may reflect on the attitude of patients to treatment outcome and most of the data on OPS and HR-QoL available reflect western thought processes. Based on the feedback of our patients we designed a simple and practical patient-reported outcome measure (PROM) questionnaire reflecting the important issues as voiced by our patients and validated it using the QQ-10, indicating good face validity and acceptability of our questionnaire. We undertook this study to understand the acceptability of OPS level I and II procedures and to determine the satisfaction with the cosmetic outcome as well as the need for contralateral symmetrization procedures in our patients. PATIENTS AND METHODS Based on patient feedback, a questionnaire (Q-IN) was developed and validated by the QQ-10. It includes 9 questions reflecting three domains of general acceptability of the procedure, satisfaction with cosmetic outcome and degree of functional impairment in terms of altered sensation. 126 patients with breast cancer who underwent OPS level I or II without contralateral symmetrization were included in the study. Q-IN was self-administered during routine follow-up, following surgery, between January 2017 and December 2018. It was validated by 31 patients (24.6%)who also answered the QQ-10, a questionnaire designed to assess patients’ views on their experience of using PROM questionnaires during their medical care. The mean value score of the Q-IN as per the QQ-10 was high (84.79%, SD 11.7%) and mean burden score was low (20.96%, SD 24.6%) indicating that it has good face validity and is relevant and acceptable to our patients.RESULTS Mean age of patients was 51 years (21-77 years) and median follow up was 41 months (2- 156 months) following OPS. Majority of patients 124 (98%) were happy about undergoing BCS and had no doubts about the procedure. Most, 115 (91%) were very happy with the cosmetic appearance (shape, size and overall appearance) of the breast after OPS, 10 (8%) were happy and 1 patient (1%) was unhappy. Although most, 103 (81.7%) women, noticed a difference in size the majority 92 (89.3%) felt it was minimal and only 8 (7.8%) found a major difference in size. Of the 78 (61.9%) women that felt a difference in shape, 63 (80.8%) felt it was minimal and 11 (14.1%) reported a major difference. The quality of life of 23 (18.3%) patients was affected by the change in shape and size of the breast. Of these 17(74 %) only thought about the change in appearance, and in 6 (26%) it made a minor difference. Breast sensation was altered in 76 (63.3%) women and that of the nipple-areola complex (NAC) in 77 (58.7%). Of them, 25 (32.9%) reported no sensation in the breast and 30 (40.5%) felt no sensation in the NAC. When asked about a contralateral symmetrization procedure on the normal breast, only 2 (2%) said they would want to undergo symmetrization surgery. CONCLUSIONS Most patients undergoing level I or II oncoplastic breast surgery are happy and satisfied with the overall cosmetic and functional outcome. Only 2% of patients would like to undergo a contralateral symmetrization procedure to match the operated breast. Citation Format: Vinay Deshmane, Anuja Raniwala, Clotilda Cardoza. Patient-reported outcome after oncoplastic breast conservation surgery using level I or II techniques without contralateral symmetrization [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-11-35.