key: cord-0837080-yryyqkn8
authors: Zhou, Jun; Liu, Yuyin; Xu, Ming; Mei, Li; Ruan, Shengnan; Zhang, Ning; Yi, Pengfei; Chen, Qianzhi; Tan, Jie
title: Management of breast cancer patients during COVID-19 pandemic: the experience from the epicenter of China, Wuhan
date: 2021-05-06
journal: Clin Breast Cancer
DOI: 10.1016/j.clbc.2021.04.014
sha: 35c0845757090e200e0f1c8b8f59cf8e190c12e7
doc_id: 837080
cord_uid: yryyqkn8

The coronavirus disease 2019 (COVID-19) pandemic is a global public health event. Wuhan used to be the epicenter of China and finally controlled the outbreak through city lockdown and many other policies. However, the pandemic and the prevention strategies had a huge impact on the medical care procedures for breast cancer patients, leading to the delay or interruption of anticancer therapies. To better serve breast cancer patients under the premise of epidemic control, many strategies have been proposed and optimized in our center. One of the most important parts of these strategies is the promotion of telemedicine, including online consultation, online prescription, and drug mailing services. In keeping with the city and hospital policies, we have also introduced stricter ward management policies and more precise care. Here, we collected the diagnosis and treatment process of breast cancer patients in our center during the COVID-19 pandemic, which was found to be correlated to a reduction in chemotherapy-related myelosuppression and hepatic dysfunction, hoping to provide a reference for other cancer centers that may suffer from the similar situation. MicroAbstract The COVID-19 pandemic has a huge impact on the medical care procedures for breast cancer patients. Here we share our experience in the management of breast cancer patients during the pandemic in Wuhan, and it is found to be correlated to a reduction in chemotherapy-related myelosuppression and hepatic dysfunction, which may provide a reference for other centers.

The coronavirus disease 2019 (COVID- 19) pandemic is a global public health event. Wuhan used to be the epicenter of China and finally controlled the outbreak through city lockdown and many other policies. However, the pandemic and the prevention strategies had a huge impact on the medical care procedures for breast cancer patients, leading to the delay or interruption of anticancer therapies. To better serve breast cancer patients under the premise of epidemic control, many strategies have been proposed and optimized in our center. One of the most important parts of these strategies is the promotion of telemedicine, including online consultation, online prescription, and drug mailing services. In keeping with the city and hospital policies, we have also introduced stricter ward management policies and more precise care.

Here, we collected the diagnosis and treatment process of breast cancer patients in our center during the COVID-19 pandemic, which was found to be correlated to a reduction in chemotherapy-related myelosuppression and hepatic dysfunction, hoping to provide a reference for other cancer centers that may suffer from the similar situation.

The COVID-19 pandemic has a huge impact on the medical care procedures for breast cancer patients. Here we share our experience in the management of breast cancer patients during the pandemic in Wuhan, and it is found to be correlated to a reduction in chemotherapy-related myelosuppression and hepatic dysfunction, which may provide a reference for other centers.

The coronavirus disease 2019 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a worldwide public health event. Wuhan was the epicenter of China and great efforts have been endeavored to control the outbreak in this city [1] [2] [3] . Wuhan announced the city lockdown on January 23, 2020, followed by a number of other policies to control the pandemic 4 . Large amounts of medical resources were also devoted to the patients with COVID-19 5 , 6 . These measures have led to the rapid control of COVID-19 in this city. Now Wuhan has passed the most difficult period and the quarantine level has been downgraded significantly. But the pandemic and the prevention strategies have had and will continue to have a huge impact on the "new normal" health care system [7] [8] [9] .

Under such an unanticipated circumstance, medical care for breast cancer patients has been postponed or interrupted during the pandemic in Wuhan. Compared to the general population, breast cancer patients are at increased risk of infection and developing worse outcomes due to the original malignancies, suppressed immunity, and therapy-related side effects 10 , 11 . Breast cancer patients in Wuhan were exposed to a high risk of delays or interruptions of standard anticancer therapy during the pandemic, due to the city lockdown and shortage of medical resources. Moreover, the treatment modalities for patients who suffered both breast cancer and COVID-19 would have been interrupted until the Health Management Program for Discharged COVID-19 Patients was met 12 .

To better serve breast cancer patients on the premise of epidemic control, many strategies have been proposed and optimized in our center, the Department of Breast and Thyroid Surgery of Wuhan Union Hospital. One of the most important parts of these strategies is the promotion of telemedicine, including online consultation, online prescription, and drug mailing services. In keeping with the city's and hospital's policies, we have also introduced stricter ward management measures and more precise care.

Here, we collected the diagnosis and treatment process of breast cancer patients in our center during the COVID-19 pandemic, which was found to be correlated to a reduction in chemotherapy-related myelosuppression and hepatic dysfunction, in the hope of providing a reference for other cancer centers that may suffer from the similar situation.

Wuhan announced the lockdown measures on January 23, 2020, followed by a number of other policies to control the pandemic, and we chose this key date as the cut-off time for our analysis in this study. We then collected the outpatient and inpatient programs for confirmed or suspected breast cancer patients in the Department of Breast and Thyroid Surgery of Wuhan Union Hospital during the pandemic. To explore the response of breast cancer patients to these strategies, we also retrospectively analyzed consecutive breast cancer patients who came to our department for chemotherapy from December 1st, 2019 to June 15th, 2020, using January 23, 2020 as the cut-off date.

Breast cancer patients who came to our department for chemotherapy underwent selective blood routine tests or liver function tests as recommended by their attending physicians. To calculate the incidence of chemotherapy-related side effects during the pandemic, we collected the results of all patients' first blood routine or liver function tests in each cycle of chemotherapy, including adjuvant chemotherapy and neoadjuvant chemotherapy. If the patient exhibits moderate or above myelosuppression or hepatic dysfunction, chemotherapy may be delayed until the results are almost normal, and the reexamination results of blood routine or liver function in this chemotherapy cycle were excluded in this study.

The results of blood routine test and liver function test were divided into the "before pandemic" group and "during pandemic" group according to their test time Hepatic dysfunction was defined as any abnormally elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT), or gamma-glutamyl transpeptidase (GGT). The normal ranges of AST, ALT, and GGT were defined as 8-40 U/L, 5-35 U/L, and 7-32 U/L, respectively.

Results of blood routine or liver function tests were compared using Kruskal-Wallis test and the abnormal data were organized by frequency (%). Pearson Chi-Square test was used to compare the categorical data between the before and during pandemic groups. Logistic regression was used to calculate the Odds Ratios The process of diagnosis and treatment of confirmed or suspected breast cancer patients during the pandemic is shown in Figure 1 . For patients in our center, we provide online consultation through a public platform of our hospital in Wechat for routine follow-up. For the patients who need oral medications, such as endocrine therapy drugs, oral chemotherapy drugs, etc., we provide the online prescription with real-name authentication and drug mailing services, which may reduce the risk related to the patients visiting the hospital. For patients who still require an on-site outpatient visit after the online consultation and prescription, including patients who need imaging and laboratory tests, patients are advised to go to the hospital with proper personal protection, as well as receiving temperature screening and epidemiological investigation before entering the outpatient center.

As shown in Figure 2A , the frequency of online consultations increased slightly after the city lockdown, while it increased robustly on the day we introduced the online prescription and drug mailing system. A total of 6720 online consultations with our center were recorded in this study, with a daily number (mean ± standard deviation) of 6.88 ± 3.65 before the lockdown and 29.38 ± 13.33 during the pandemic ( Figure 2B , P<0.001).

For patients requiring hospitalization for surgery, periodic chemotherapy, radiation, or targeted therapy, careful pre-hospital COVID-19 screening is recommended. To reduce the patients' financial burden, the city residents' health insurance covers most of the costs of the above screening methods. As shown in 

We collected the clinicopathological characteristics of all patients who came to our center for chemotherapy from December 1st, 2019 to June 15th, 2020, using January 23, 2020 as the cut-off date. A total of 358 patients were included in this study and they were divided into two groups based on when they were diagnosed with breast cancer. There were 6 patients among them suffered COVID-19 and had been cured. As shown in Table 1 , 177 patients were diagnosed before the pandemic, and 181 were diagnosed during the pandemic. Characteristics of the patients are compared between these two subgroups. There are some significant differences in molecular subtype (P<0.001), but no significant differences are found between the age at diagnosis, T stage, N stage, M stage, chemotherapy regimen, targeted therapy, and radiation. As for the difference in surgery regimen, it might be since a proportion of patients diagnosed during the pandemic were still undergoing neoadjuvant chemotherapy until June 15th, 2020. While most of the patients diagnosed before the pandemic had finished neoadjuvant chemotherapy, except for a few patients with advanced breast cancer who were not suitable for surgery. To reduce the risk related to frequent hospital visits of the patients, we reduced the use of weekly chemotherapy schedules (2.8% versus 0%, P=0.023).

To calculate the incidence of chemotherapy-related side effects during the pandemic, we collected the blood routine and liver function test results of 358 breast cancer patients receiving chemotherapy. None of these patients had been diagnosed with liver metastasis or active hepatitis. These patients had a median (range) age of 49 (25-77) years old and the median (range) number of chemotherapy cycles during the time of our study was 4 (2-10). The blood routine and liver function tests were performed according to the patient's condition and the doctor's consideration. No severe myelosuppression and liver dysfunction were observed in this study.

The blood routine test results are summarized in Table 2 . Within the whole period included in this study, we collected 495 results of blood routine tests before the pandemic and 906 during the pandemic. As shown in Table 2 , there is no significant difference in the exact counts of white blood cell (WBC) and neutrophil (NE) between these two periods, while the platelet (PLT) counts decreased slightly but still pretty much in the normal range. However, the incidence of leukopenia (16.6% versus 12.4%, P=0.029) and neutropenia (10.1% versus 7.1%, P=0.047) both decreased significantly. Though there is no significant difference in thrombocytopenia, the incidence of thrombocytopenia decreased slightly (7.1% versus 5.4%, P=0.210). To calculate the Odds Ratios (ORs) between these two periods, univariate logistic regression was performed. As shown in Table 3 

A total of 444 liver function tests are included in this study, 247 were performed before the pandemic and 197 during the pandemic. As shown in Table 4 , there were significant reductions in levels of both aminotransferase (AST) (P<0.001) and alanine aminotransferase (ALT) (P=0.012) during the pandemic. The incidence of hepatic dysfunction (45.3% versus 34.0%, P=0.016) and ALT elevation (37.2% versus 20.3%, P<0.001) both decreased significantly. The incidence of AST elevation decreased slightly with no significance (16.2% versus 13.2%, P=0.378). As shown in Table 5 , 

To the best of our knowledge, few studies 13 have shared their preparedness plans for the care of breast cancer patients during the COVID-19 pandemic, especially in an epicenter like Wuhan. In this study, we described the strategies of breast cancer in our center. We have made the above adjustments to the management of breast cancer patients without compromise to the long-term oncological outcomes, and the incidence of chemotherapy-related myelosuppression and hepatic dysfunction was even significantly decreased during the pandemic.

There are two key points that need to be considered during the pandemic according to the severity of the pandemic, local policies, and the patients' condition.

One key point is the balance between hospital visits and the risk of exposure to SARS-CoV-2, and another is the balance between side effects induced by anticancer treatments and the risk of poor outcomes once the patient got infected 14 , 15 . A review from Singapore 16 suggested a universal framework and it may be applied to pandemic planning guideline development in other parts of the world. The specific strategies in different areas may differ, but common topics include classification of patient prioritization, minimizing hospital visits, telemedicine, and modifying acceptable managements 17, 18 .

Online consultation is an important part of telemedicine, but its capabilities are relatively limited. With our data, we demonstrated that even after the city lockdown, the number of online consultations has increased only by a small margin. The online consultation system can only realize the communication function, but not the physical examination, or imaging or laboratory tests, or prescription or pharmacy. In addition to answering patients' questions and relieving anxiety, more practical value of telemedicine is online prescription and drug delivery services. For patients with chronic diseases, such as malignant tumors, this system can significantly reduce the need to go out for medical care services and purchase drugs, thus reducing the possibility of their exposure to COVID-19 infection risk. However, online prescription and drug delivery services require policy support from the government and competent administrative departments for health 20, 21 . These administrators need to strike a balance between the needs of patients and important issues such as drug safety. This may be an important development direction for telemedicine services in the future.

Thanks to China's adequate medical resources, in our center, all the screening tests can be completed in one day or even six hours for certain cases. Rapid and comprehensive screening makes it easier for patients to get proper medical care on the premise that reduces the risk of COVID-19 infection. No nosocomial infection of COVID-19 was reported in our center since the strict screening strategies were taken during the pandemic. As the pandemic rapidly spreads and changes, we recognize that our recommendations in this study should be optimized based on the specific situations of other medical centers. In the absence of sufficient medical resources to ensure rapid and adequate screening, hospital administrators need to comprehensively assess the need for anticancer treatment and the potential risk of COVID-19 in cancer patients, and then adjust the screening procedures.

The main measures to control an epidemic are to control the source of infection, cut off the transmission route, and protect the susceptible population [21] [22] [23] . Cancer patients as a special susceptible group need special care during the pandemic. It is suggested by many oncologists that a designed postponing of elective surgery, cytotoxicity chemotherapy, or immune checkpoint inhibitors for some stable cancer could be considered in high-risk areas [24] [25] [26] . A survey of 343 oncologists from 28 countries also indicated that most participants would use less aggressive therapy to avoid potential risk during the pandemic 27 . For patients receiving periodic chemotherapy in our department, we appropriately changed the diagnosis and treatment strategies according to the actual condition. Although some measures have not been documented or quantified, we still found significant reductions in chemotherapy-related side effects during the pandemic. The reduction may be correlated to ward visit limitation, or less use of weekly chemotherapy schedule, or more use of long-acting granulocyte-colony stimulating factors (G-CSF), or masks, or strengthened public health awareness, or other potential factors. Limited by our working conditions, we were not able to record detailed information including patients' other clinicopathological information, therapeutic drugs and doses, other chemotherapy-related side effects, and long-term follow-up. These lead to limited findings on the specific and elaborate relationship between the measures we took during the pandemic and the therapeutic response of the patients.

Considering the current situation and development trend of COVID-19 all over the world, it is difficult to assess its final impact and consequences. This pandemic has brought great challenges in the management of those who are infected or affected.

In this study, we collected the diagnosis and treatment process of breast cancer patients in our center during the COVID-19 pandemic, in the hope of providing a reference for other cancer centers that may suffer from a similar situation. And we further analyzed the short-term chemotherapy-related side effects of breast cancer patients, as a result of the current strategies, which have never been reported, detailed follow-up for long-term outcomes is still crucial.

The authors announced no conflict of interest.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

JT., JZ, and YL designed the study; JZ, LM, NZ, SR, NZ, PY, and QC collected the data; JZ and YL analyzed the data; JT and JZ completed the manuscript, and all authors approved of the manuscript. 

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