The immunohistochemical classification of breast cancer into luminal (HR+), HER2 and TN tumors [26–28] allows different treatment strategies to be adopted. In TN and HER2 tumors, NACT regimens and/or associated target therapy, even in EBC, have contributed to minimizing surgical morbidity and to identifying patients with residual disease for additional adjuvant therapy [29–31]. On the other hand, the approach with luminal tumors is generally upfront surgery, with the need for chemotherapy being defined according to histopathology, immunohistochemistry and genomic assay . In general, the use of NET has been restricted to exceptional cases .
The COVID–19 pandemic has affected the world at different moments, requiring the reorganization of health structures [2–4]. Cancer patients are at an increased risk of contagion, infection, morbidity and death [9–11]. Emergency guidelines for breast cancer treatment [13–15,32,33] have suggested postponing surgery when the risk of progression is low (luminal tumors), initiating NET, extending the application of NACT and/or target therapies to subtypes of adverse biology (TN and HER2), minimizing the extent of surgery, including avoiding the use of autologous tissue in breast reconstruction, and postponing prophylactic surgery.
Brazil is a country of continental dimensions, with widely differing distribution of human and technical resources. The availability of hospital supplies and beds is greater in the southeast of the country where the concentration of COVID–19 cases is greater [34,35]. The concentration of physicians affiliated to the SBM is also greater in the southeast, with the highest response rate in the present study (48%) being from that region, followed by the northeast, the south, the Midwest and finally the north, with only 3%. In agreement with the SBM database, most respondents live in state capitals or in cities with more than 500,000 inhabitants, which are also those most affected by COVID–19 .
The onset of the COVID–19 epidemic in Brazil occurred relatively late compared to Europe and North America. Whereas the incidence of the disease was high in Italy and Spain in March, it was only beginning to appear in Brazil at that time, first in the city of São Paulo (southeast), and then spreading unevenly throughout the country . This heterogenous pattern of spread may have resulted in poorer initial compliance by Brazilian breast specialists with the guidelines issued in those countries. Accordingly, 57% of participants had not changed EBC management at the beginning of the pandemic, while 70% had changed management during the course of the pandemic. At the beginning of the pandemic, changes in management occurred similarly in both sexes and in the different age groups, and irrespective of board certification or workplace. The demographic characteristics most associated with change in management at the beginning of the pandemic were living in the southeast of the country and in a state capital city, coinciding with the areas in which the incidence of COVID–19 infection was greatest, with increasing demand for hospital beds and implementation of government restrictive measures. On the other hand, during the pandemic, various state capital cities made an effort to reserve COVID-free hospitals or wards so as to guarantee the admission of elective patients, particularly cancer patients. These initiatives, however, had no effect on the results of this survey.
NET was more commonly indicated for postmenopausal women, both in the case of luminal A (48%) and luminal B tumors (34%). For premenopausal women, the specialists were more likely to recommend NET for cases of luminal A (18%) compared to luminal B tumors (11%). Menopausal status had a significant effect on how these specialists manage EBC. Conversely, although a considerable proportion of respondents suggested a different approach with respect to luminal tumors, upfront surgery remained the most common choice. For premenopausal women, 77.5% of respondents recommended upfront surgery for luminal A tumors and 67% for luminal B tumors. For postmenopausal patients, fewer respondents would recommend upfront surgery, either for luminal A tumors (50%) or for luminal B tumors (52.5%). The pandemic and the emergency recommendations for EBC treatment impacted on the management strategies of Brazilian breast specialists. According to these recommendations [13–15,24,32,33], HR-positive EBC should preferentially be treated using NET. Some societies have suggested that recommendations for the treatment of EBC should be classified by degree of priority according to the advice provided in the Ontario Health Pandemic Planning Clinical Guideline for Patients with Cancer , with cases of luminal tumors being classified as Priority B and surgery being postponed for 3–6 months. Another cancer organization also suggested that luminal A tumors should be treated initially with NET, while in the case of luminal B tumors, particularly those in which the axilla is positive or clinical stage II, the use of genomic assays could be useful in making this decision [33,38,39]. On the other hand, despite the partial compliance of Brazilian breast specialists with NET, particularly in cases in which the proliferation index is low, it is clear that a good proportion of those interviewed are still reluctant to use this strategy, even in exceptional conditions such as during a pandemic. However, although NET is a treatment that remains under debate, its use has increased in recent years with the publication of studies showing its safety [16–18,40,41].
In HER2 and TN tumors, considerable variations were found in the protocols from the different organizations. In one, TN and HER2 tumors are classified as Priority B1, suggesting NACT for tumors over 2 cm or with affected axillae . Others also suggest NACT without specifying the cut-off point for treatment [32,33]. The Brazilian Society of Clinical Oncology suggests NACT for tumors over 5 mm or in the case of positive axillae .
These differences were reflected in this survey, with 21% of participants recommending NACT for all cases of HER2 tumors and 19% for all TN tumors. Overall, 40% of respondents considered the cut-off point of 1 cm for an indication of NACT to be appropriate in the case of HER2 tumors, while 43% deemed it appropriate for TN tumors. Conversely, 12% considered a cut-off point of 0.5 cm to be appropriate for NACT in HER2 tumors and 15% for TN tumors. In these subtypes, compliance with the recommendations would appear to be greater, although it is impossible to affirm that there was indeed any change. The prediction of a better pathological response to cytotoxic drugs and targeted therapy, as well as the possibility of selecting cases of residual disease for additional adjuvant therapy, had already rendered neoadjuvant therapy the standard treatment in many cases before the pandemic [29,30,42]. Likewise, in our understanding, the fact that one-third of respondents opted for NACT in cases of tumors <1 cm may represent overtreatment, since there are safe options of de-escalating treatment, as occurs in cases of HER2 tumors .
Breast reconstruction constitutes the basic principle in the present-day surgical treatment of breast cancer, reducing the patient’s sensation of mutilation and improving their quality of life [44,45]. Approximately 60% of the participants would recommend total immediate breast reconstruction, with the most commonly suggested technique being definitive implants, followed by tissue expanders and autologous tissue. For breast-conserving surgery, 75% would recommend partial reconstruction, whereas 54% would contraindicate mammoplasty. Finally, 85% of respondents would not recommend risk-reducing mastectomy for patients with BRCA deleterious mutations. These data agree with the recommendations to avoid or delay major surgery that could prolong hospitalization and increase complications or require further hospital admissions [46–52].
There are some limitations associated with the present study. Since the data originate from a survey, it is impossible to affirm that the behavior encountered in these results would be completely applicable in practice. In addition, the deadline established for the responses to the questionnaires to be received was short; however, the dynamics of the progression of the pandemic could have affected the results if this time had been longer. Nevertheless, the short deadline may have affected the response rate of 34.4%, increasing the likelihood of bias. On the other hand, no significant differences were found between the different geographical regions of the country, or between the SBM database and our sample population, leading us to believe that the sample was indeed representative.