Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase Ⅱ single-arm study

Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin(PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2(HER2)-positive early breast cancer(BC).Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD(30-35 mg/m^(2)) and cyclophosphamide(600 mg/m^(2)), followed by four cycles of taxanes(docetaxel,90-100 mg/m^(2) or nab-paclitaxel, 260 mg/m^(2)), concomitant with eight cycles of trastuzumab(8 mg/kg loading dose,then 6 mg/kg) and pertuzumab(840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response(tp CR, yp T0/is yp N0). Secondary endpoints included breast p CR(bp CR),objective response rate(ORR), disease control rate, rate of breast-conserving surgery(BCS), and safety(with a focus on cardiotoxicity).Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42(53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval(95% CI), 48.5%-71.2%] patients achieved tp CR, and 49(62.8%) achieved bp CR. ORRs were 76.9%(95% CI, 66.0%-85.7%) and 93.6%(95% CI,85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine(11.5%) patients experienced asymptomatic left ventricular ejection fraction(LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP(NT-pro BNP), troponin I, or high-sensitivity troponin.Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile,especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.

Comparison of breast-conserving surgery and mastectomy in early breast cancer using observational data revisited:a propensity score-matched analysis

Recent observational studies showed that breast-conserving surgery(BCS) resulted in superior survival compared to mastectomy in breast cancer patients. This study compared the clinical outcomes of BCS and mastectomy using propensity score(PS)matching analysis, which had advantages over conventional methods in reducing bias. Nonmetastatic breast cancer patients who underwent BCS and mastectomy were matched 1:1 based on their PS. We used the Kaplan-Meier method and Cox-regression model to estimate the treatment effects. A total of 2,866 patients with a median follow-up time of 67 months were included in the original study population. Although the mastectomy cohort(N=1,219) had more advanced disease compared to the BCS cohort(N=1,647), LRFS was similar between the two groups(93.8% vs. 92.4%, P>0.05). BCS(vs. mastectomy) was associated with improved DFS(73.8% vs. 58.7%, P<0.01) and CSS(91% vs. 78.2%, P<0.01) in the original population. In the PS-matched population(N=1,668), clinicopathological features were equally distributed between the two cohorts. BCS(vs. mastectomy) was not associated with improved DFS(70.7% vs. 66.9%, P>0.05) or CSS(87.5% vs. 84.9%, P>0.05). We found that PS methods reduce bias when estimating treatment effects using observational data. BCS and mastectomy show equivalent outcomes in nonmetastatic breast cancer patients.

In pursuit of a flawless aphrodite:paving the way to scarless oncoplastic breast surgery

Introduction Breast cancer is the most commonly diagnosed malig-nancy in women worldwide[1,2]and in the twentieth century,mastectomy was the primary surgical treatment for breast cancer patients.Advances in breast-conserving surgery(BCS)propelled a change in treatment rational from“maximum tolerable”to“minimum effective”ther-apy.Oncoplastic breast surgery aims to restore the shape of the breast and has been widely adopted since the past decade.Although the cosmetic outcome has been sig-nificantly improved,the scar remaining on the surgeried breast skin is still a major pitfall that urges urgent consid-eration.In this editorial,we review a series of techniques that can be incorporated in oncoplastic breast surgery to minimize scarring,signifying the beginning of an era for scarless oncoplastic surgery.