Cancer Research, Statistics, and Treatment

: 2022  |  Volume : 5  |  Issue : 1  |  Page : 152--153

Authors' reply to Agarwal et al. and Iyer

Ajeet Kumar Gandhi1, Ajay Gogia2,  
1 Department of Radiation Oncology, Dr RMLIMS, Lucknow, Uttar Pradesh, India
2 Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India

Correspondence Address:
Ajay Gogia
Department of Medical Oncology, IRCH, AIIMS New Delhi - 110 029

How to cite this article:
Gandhi AK, Gogia A. Authors' reply to Agarwal et al. and Iyer.Cancer Res Stat Treat 2022;5:152-153

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Gandhi AK, Gogia A. Authors' reply to Agarwal et al. and Iyer. Cancer Res Stat Treat [serial online] 2022 [cited 2022 Jun 25 ];5:152-153
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We thank Agarwal[1] and Iyer[2] for their critical appraisal and comments on our article titled, “Correlation of pathological complete response with outcomes in locally advanced breast cancer treated with neoadjuvant chemotherapy: An ambispective study.”[3],[4]

Neoadjuvant therapy in locally advanced breast cancer (LABC) has been evolving over the past two decades. LABC includes a spectrum of diseases ranging from operable stage III disease to inoperable non-metastatic LABC owing to advanced primary or nodal disease. With growing awareness, the proportion of patients with very advanced inoperable non-metastatic LABC is on the decline. The intent of neoadjuvant therapy varies as per the institutional disease management group policies, and presently, the focus is on tailoring treatment regimens according to the molecular subtypes of breast cancer.

The use of neoadjuvant concurrent chemoradiotherapy (NACRT) is not new and has been tried sporadically for a long time. With the advent of more effective anthracycline- and taxane-based neoadjuvant chemotherapy regimens and now with the incorporation of anti-HER2-based targeted therapy, the role of NACRT has diminished further. In the study by Shanta et al.,[5] the authors used concurrent cyclophosphamide, methotrexate, and fluorouracil; and cyclophosphamide, epirubicin, and fluorouracil along with radiotherapy, and reported primary tumor downstaging in approximately 45% of the cases. The definition of pathological complete response (pCR) was not very stringent, and application of the modern criteria to the previous study may have yielded a lower pCR rate. Moreover, toxicities were not well reported in the study. It is known that concurrent anthracycline with radiotherapy leads to exacerbated acute and delayed radiation toxicity. In addition, the adjuvant systemic therapy have evolved evolved and the treatment regimens used in the study are no longer the standard of care.

On the other hand, the study by Iyer et al.[6] included patients with only inoperable LABC (pectoralis muscle infiltration, ipsilateral supraclavicular, internal mammary lymph nodal involvement, fixed axillary lymph node, etc.) and concurrent taxane (paclitaxel 175 mg/m2) with neoadjuvant radiotherapy, either before or after anthracycline-cyclophosphamide chemotherapy, was used. Grade 3 skin toxicities were observed in 24% of the patients and post-operative wound infection in 14%; 26% received filgrastim for neutropenia during NACRT. The authors reported pCR rates of 54% and 34% in TNBC and HER2/neu-positive patients, respectively, which is impressive (as compared to our study where the pCR rate was 31%). However, it came at the cost of added toxicity. Similarly, higher surgical complication rates (41%) and higher Grade 3 skin toxicities (50%) have been reported with NACRT by Skinner et al.[7] and Kao et al.,[8] respectively. Concurrent administration of taxane with radiotherapy may also be associated with a higher risk of pneumonitis, which may be reduced by adjusting and modifying the regimen of concurrent chemotherapy as done in the study by Formenti et al.[9] In this study, the authors suggested the use of twice weekly paclitaxel at a dose of 30 mg/m2. While these regimens appear to be cost-effective, toxicities could negatively affect the secondary breast reconstructive options. NACRT may be suitable for a select group of patients with very advanced LABC. Future prospective studies would help define its role better.

NACRT is not the only novel approach for neoadjuvant treatment, and the recent incorporation of platinum-based neoadjuvant chemotherapy in TNBC[10],[11] and dual anti-HER2/neu blockade[12] have led to pCR rates exceeding 50%–60%. These novel neoadjuvant treatment strategies are not associated with increased toxicities, are well tolerated, and may lead to better survival. Some of these regimens, like platinum for TNBC, are also cost-effective in resource-constrained settings. Thus, patient morbidity and survival outcomes need to be finely balanced by tailoring the treatment. This obviously does not mean that neoadjuvant radiotherapy does not have a role in the management of breast cancer. There is a renewed interest in the role of pre-operative radiotherapy in breast cancer. Excellent 5-year cosmetic and local control rates have been reported in the pre-operative accelerated partial breast irradiation (APBI) trial,[13] and novel protocols with single fractionated dose-escalated pre-operative APBI are under evaluation.[14] The tolerance of neoadjuvant radiotherapy alone is better as compared to NACRT regimens.

The question of the optimal induction regimen, i.e., NACRT versus neoadjuvant chemotherapy or pre-operative radiotherapy can only be answered with planned randomized controlled trials. The NeoRAD trial is planning to evaluate pre- versus post-operative radiotherapy in breast cancer.[15] Randomized controlled trials comparing NACRT with neoadjuvant chemotherapy can reliably answer this question, but until then, individualized and tailored neoadjuvant chemotherapy should remain the standard of care.

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Conflicts of interest

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