Response assessment in triple positive breast cancer with neoadjuvant chemotherapy and targeted therapy: A case report and its literature review of different regimes, targeted drugs, immune therapies, bispecific antibodies which are under trials

Abstract

Background: Triple positive breast cancer expresses the human epidermal growth factor receptor (Her 2 neu), estrogen and progesterone receptor. It is well known that Her 2 neu expression is associated with a more aggressive subtype of breast cancer and is associated with reduced mortality. It has less response to hormonal therapy. Neoadjuvant chemotherapy and targeted therapy have become the new standard of treating Her 2 expressive or Triple positive breast cancer. Introduction: Triple positive breast cancer is a subtype of breast cancer having expression of Estrogen receptors, progesterone and Her 2 neu receptors. The current standard of this in localized disease (stage I, II and III) includes neo adjuvant targeted along with chemotherapy. The response rate of different regimens in neo adjuvant settings varies widely. Choosing of neo adjuvant treatment depends on patient performance status, comorbidities and socio-economic status. Objective: To find the percentage of size reduction in triple positive breast cancer, in neo adjuvant Chemotherapy and targeted agents and assess for pathological complete response rates. Study Design: Case report and its systematic review. Methodology: Got the patient data with informed consent from patients treated at Khyber Teaching hospital Peshawar, and compared with the data already published in PubMed library, Google scholar. Up to date chemotherapy protocols have been followed as advised in the national comprehensive care network (NCCN). Extensive Literature search has been mentioned with sophisticated drugs and under trials regimen with referencing done. Results: Her 2 expressive disease or triple positive breast cancer is one of the aggressive histological subtypes and its treatment is one of the most costly treatments due to the involvement of the targeted therapy against Her 2 neu receptors. In our case we had a very huge left breast cancer which was Her 2 neu positive. She received neo adjuvant chemotherapy along with Herceptin and perjeta, to which the cancer had responded very well, and down staged the disease from in operable to make it operable and the patient underwent surgery followed by adjuvant radiation therapy and Hormonal as well as chemotherapy and targeted therapies as received in neo adjuvant setting. As per the different trials the pathologic complete responses (p CR) have been found to be different like Neosphere the pCR was 46%, TRYPHAENA showed pCR rates in all treatment arms ranging from 57% to 66%, ACOSOG (p CR= 55%), NSABP (p CR= 49%), GBG (p CR= 45%), DAPHNE (p CR= 56.7%), ADAPT (p CR= 40%), PAMEL (p CR= 30%), GEPARSEPTO (p CR= 60%). In targeted agents Trustuzumab DM TDM 1, PERTUZUMAB showed 43.6% (95% CI, 33-52%) overall response rate, DHP regimen in CLEOPTRA shows PFS of 18 months and median OS of 57 months. Trastuzumab Deruxtecan and DS-8201 showed 59.5% (95%CI, 49.7–68.7) over all response rate, The PFS was 19.4 months (95%CI, 14.1–not reached), 24.6 months (95%CI 23.1 months-not reached) of median OS. ARX788 showed PFS of 17 months if use as monoclonal agent in met breast Cancer. Neratinib showed PFS of 22.2 weeks if used trustuzumab if no trustuzumab than 39 week PFS and OR rate of 24% if previously trustuzumab used if no trustuzumab used than ORR of 54 %. Pyrotinib and poziotinib showing PFS of 14.1 months, ORR of 27%, PFS of 4 months (95% CI, 3.0-4.4) respectively. CDK4/6 inhibitors showed no objective response if used as a mono therapy Monarch Her trial showed ORR (35.4% vs. 22.8% with chemotherapy plus trastuzumab) and median PFS with the endocrine/targeted therapy triplet (8.3 vs. 5.7 months; HR = 0.673, 95%CI, 0.451–1.003; p = 0.0253) but no significant response difference with no chemo arm and and PI3K Inhibitors Llike Alpelisib with TDM 1 shows response in pre-treated HER2-positive patients, an ORR of 43% and a median PFS of 8.1 months (95%CI 3.9–10.8) were reported. In the BOLERO-3 trial, the combination of everolimus with trastuzumab and vinorelbine was evaluated in patients with trastuzumab-resistant ABC, and a small but statistically significant benefit in PFS was reported: median PFS 7.0 vs. 5.78 months (HR = 0.78; 95%CI, 0.65–0.95; p = 0.0067). Margetuximab plus chemotherapy generated handsome amount of 24% relative risk reduction in the hazard of progression vs trastuzumab plus chemotherapy, median OS was 21.6 months with margetuximab vs 19.8 months with trastuzumab, and the final analysis of OS will be reported. Conclusion: The results of all the trials have been discussed briefly along with a case report to signify the treatment in aggressive type of breast cancer. The treatment has been standardized, for tumors of size less than 2 cm shall undergo upfront surgery, followed by adjuvant treatment. If it is pathologically T1 with no nodal metastasis then the patient is advised to receive HP for 12 cycles as per Tolaney study, but if it is p T2 or N+ than the patient will be treated by chemotherapy along with HP for 12 cycles as per Aphinity trial. Those patients having tumor size greater than 2 cm or having nodal metastasis shall receive neo adjuvant chemotherapy and targeted therapy followed by surgery. Adjuvant treatment is based on the final histology of pCR than HP for one year as per Aphinity trial. If no p CR then the patient is advised to receive radiation therapy along with Trastuzumab emtansine (TDM-1) for one year as per Katheriene trial or shall receive HP for 6-12 cycles followed by Neratinib for one year as per Extenet trial.