With the rapid progression of COVID-19 worldwide, it is inevitable that large numbers of cancer patients will be affected by this pandemic [5-10]. This leads to grave concerns about standard-of-care treatment regimens in COVID-19 era and the adoption of protective measures, such as postponing active cancer treatments. However, it is impossible to provide a set of universal guidelines for all types of cancer, especially for patients receiving active life-saving therapy or undergoing active treatment to achieve a probable cure. Breast cancer, the most common malignancy among women, is commonly identified in early stages, with slow progression and high chance of cure [17]. Based on our recent report, we focused on effects of COVID-19 on breast cancer patients and determined risk factors for severe COVID-19 in this population.
By now, several studies for epidemiological characteristics of COVID-19 in cancer patients have been published, but most of them focused on general cancer patients, only two reports for breast cancer [5-10, 14, 18]. Remarkably, breast cancer patients with COVID-19 had lower disease severity and mortality when compared with general cancer patients. Compared with the similar works of breast cancer patients with COVID-19 in the world, the mortality in our study was 6.7%, which is similar to that in Vuagnat’s study(6.7%) and higher than Kalinsky’s study(3.7%) [14, 18]. These different outcomes among breast cancer patients could be explain by the different regional distribution and availability of medical cure, testing methods, subtypes and virulence of SARS-CoV-2. A current report indicated the SARS-CoV-2 variant with Spike D614 to G614 increased the infectivity of the COVID-19.[19] However, the mortality of our study (6.7%) was much lower than that of general cancer patients (11.4-18.6%) [5, 8-10]. Besides, as to disease severity, 26.7% of breast cancer patients in our study had severe disease, which still lower than that of general cancer patients observed by H. Zhang (47.8%), Ma (54.1%), and Dai (34.3%) [7, 8, 20]. In addition, there was a similar trend in the comparison of critical case rates. 8.9% (4/45) breast cancer patients developed events of admission to ICU/ mechanical ventilation/ death in our study, lower than that of general cancer patients in study of L. Zhang (53.6%), and Liang (39%) [5, 6]. The discrepancies above may be due to different strategies for combating the pandemic, cancer types, basic characteristics (e.g., sex, age, general health and comorbidities), etc. Taken together, cancer type seems to be a major determinant of mortality rate, and we can speculate that breast cancer patients with COVID-19 have better outcomes than that of general cancer population.
It seems that recent sessions of chemotherapy or other anti-cancer treatment are a risk factor for the severity of COVID-19 in cancer patients [5, 6, 9]. A study by L. Zhang indicated that undergoing anti-cancer treatment within 14 days mattered [6], and our previous study showed chemotherapy within 4 weeks was a risk factor for fatal outcomes [9]. Notably, in this study, we observed breast cancer patients undergoing chemotherapy within 7 days were more likely to get severe disease, not 2 or 4 weeks. This discrepancy of timing may be due to different cancer types, anti-cancer strategies and intensities. Breast cancer patients are generally female, relatively young, with no history of smoking [17, 21-23], indicating a better baseline condition. Moreover, they are relatively treated with mild chemotherapy regimens, in which induced haematological disorders resolve in approximately one week [24]. Breast cancer patients have been reported with better prognosis and faster recovery form chemotherapy when compared to those with other solid tumor, such as lung cancer [25].Our study focus on the relationship between anti-tumor treatment and disease severity of breast cancer patients with COVID-19. Remarkably, according to deliberate univariate and multivariate analysis, our study identified the risk and effect of chemotherapy to severe COVID-19 in breast cancer patients, reaching a profound and meaningful conclusion and emphasizing the effect of cancer therapy. Noteworthy, in Vuagnat’s study, univariate analysis showed that the ongoing cancer therapy (within 30 days) was not associated with disease severity, and there were no further analysis into cancer therapy within 7 or 14 days. Besides, the number of patient events in their study was too small to have multivariate analysis[14]. In addition, our study demonstrated the age over 75 as a distinct risk factor of severity, which shared a similar results with Vuagnat’s report (age over 70).
Laboratory examinations on patients undergoing chemotherapy within 7 days showed distinct abnormalities in infection indicators (neutrophil counts, CRP, LDH, procalcitonin) compared with those not receiving chemotherapy within 7 days, which consistent with laboratory changes found in severe patients to a rather large extent. It has been reported that neutropenia is linked to chemotherapy effects of myelosuppression [26-28], which in turn worsens the immune condition. Additionally, the immunosuppression by chemotherapy possibly prolonged the time of viral shedding [29], which provided an explaination for our study, indicating chemotherapy within 7 days led to myelosuppression and secondary infection, resulting in an aggravated illness and poor outcome of COVID-19.
Therefore, our results can serve as a basis for proposing some recommendations for oncologists. Since intravenous chemotherapy has been identified as a potential risk factor, oral chemotherapy agents [30-33] or other treatment including radiotherapy, surgery and endocrinotherapy should preferentially be administered to contain tumor progression. If active chemotherapy must be administered, measures should be taken under strict assessments of individuals, for example, less-toxic agents in myelosuppression [34-37], intensive examinations before and after chemotherapy, prophylactic administration of G-CSF [38-40], and close monitor for any symptoms indicative of SARS-CoV-2 infection for at least 7 days.
To the best of our knowledge, this is the first report of clinical characteristics and risk factor analysis for breast cancer patients with COVID-19 in Asia. However, this study has several limitations. First, the sample size of 45 cases was somehow insufficient to be significant or skewed in some respects. Only two patients received targeted therapy, which was too limited to be analyzed in multivariate models. Thus, more patients undergoing anti-cancer treatment should be included, especially those with targeted therapy. Second, this study did not delve into different regimens of chemotherapy, and extended follow-up and close observation are recommended. In addition, how to balance a delay in cancer treatment against the risk of contracting COVID-19 remains unsettled.