|Year : 2020 | Volume
| Issue : 5 | Page : 35-39
Systemic therapy for breast cancer during SARS-CoV-2 pandemic
Santosh Kumar Chellapuram, Ajay Gogia
Department of Medical Oncology, Dr. B.R.A. Institute-Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
|Date of Submission||04-Apr-2020|
|Date of Decision||06-Apr-2020|
|Date of Acceptance||07-Apr-2020|
|Date of Web Publication||25-Apr-2020|
Department of Medical Oncology, Dr. B.R.A. Institute-Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi
Source of Support: None, Conflict of Interest: None
The global community is currently facing the unprecedented challenge of the coronavirus disease 2019 (COVID-19) pandemic. More than 1 million cases have been reported until now. Increased mortality is reported in patients who are older and have cancer and multiple comorbidities. Few retrospective analyses of COVID-19 in cancer patients showed a higher mortality of about 28.6%; additionally, severe events are more in patients who develop infection within 2 weeks of receiving anticancer treatment. Clinical data separately analyzing breast cancer patients are lacking. Until an effective drug/vaccine develops, the clinical management is supportive, and pandemic control lies in non-pharmacologic interventions such as social distancing, testing, tracing, isolation, and quarantine. These measures hinder the proper care of breast cancer patients in all the three domains of clinical care, education, and research. These desperate circumstances need desperate measures. In this review, we highlight the medical management of breast cancer during this pandemic. An adoptive strategy is the need of the hour to balance both cancer care and COVID-19 management.
Keywords: BRCA, breast carcinoma, chemotherapy, coronavirus, COVID-19, India, SARS-2, SARS-CoV-2
|How to cite this article:|
Chellapuram SK, Gogia A. Systemic therapy for breast cancer during SARS-CoV-2 pandemic. Cancer Res Stat Treat 2020;3, Suppl S1:35-9
| Epidemiology|| |
In late December 2019, there was an emergence of a cluster of viral pneumonia cases in the Hubei province of China. This emergence was linked to the wet markets in Wuhan city and identified to be caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The sequencing of ribonucleic acid (RNA) has provided clues to possible origin in bats and pangolins, which later jumped species and infected humans. As coronavirus is an RNA virus, owing to its error-prone replication, there are frequent mutations resulting in antigenic variation and emergence of major epidemics such as the severe acute respiratory syndrome in 2002, Middle East respiratory syndrome (MERS) in 2012, and the current coronavirus disease 2019 (COVID-19) pandemic. As of April 2, 2020, there were approximately 1 million cases and 50,000 deaths across the globe due to COVID-19.
In India, the first case of COVID-19 was reported on January 30, 2020. The infection gradually established its hold in the entire country and as of April 2, 2020, there were 2069 confirmed cases and 53 deaths. India is in the early stage of the epidemic, but stochastic modeling shows that in the absence of implementing any specific measures, there would be over 364 million cases and 1.56 million deaths. With effective measures, this burden could be decreased to 241,974 (±33,735) total infections and 1081 (±169) deaths. In the absence of both an effective vaccine and a drug, the essence of management consists of non-pharmacologic interventions such as social distancing, testing, tracing, isolation, and quarantine. SARS-CoV-2 infection causes a spectrum of presentations varying from asymptomatic infection to severe acute respiratory distress syndrome, resulting in death. In the majority of cases (80%), the infection causes mild illness. In about 15% of cases, it causes severe illness requiring hospital stay and 5% of infectious require intensive care. The case fatality rate (CFR) reported is around 2.3%., In patients who are older and have comorbidities such as diabetes, cancer, and chronic cardiac, pulmonary, and renal conditions, immunosuppression disproportionately increases the CFR. The CFR is as high as 18.4% for persons who are older than 80 years.
| Coronavirus Disease 2019 and Cancer|| |
The clinical course of COVID-19 depends on the age of the patient and the presence of comorbidities. Cancer, by itself and by virtue of its therapy, either chemotherapy or surgery, lowers the host immunity and increases the severity of COVID-19. During previous epidemics of coronavirus as well, cancer patients had poor outcomes. A retrospective analysis of MERS infection in cancer patients in Riyadh during the outbreak of June 2015 showed a CFR of 84.2%, whereas the CFR in nononcology patients was 35%. Out of 19 patients, only 3 patients survived who had early-stage cancer. During the current pandemic, two retrospective studies have been reported from China. In an initial study of 18 patients, lung cancer was the major subtype which constituted about 28% (5/18 patients), whereas 3/18 (16.6%) patients had breast cancer. Of the 16 patients with known treatment status, 4 had received treatment for cancer in the recent past, whereas 12 patients were in routine follow-up. Cancer patients with COVID-19 were observed to have a higher risk of severe events (admitted to the intensive care unit [ICU] and requiring invasive ventilation or death) compared to patients without cancer (39% vs. 8%, P = 0.0003). Another retrospective analysis of 28 cancer patients showed poor outcomes: 53.6% had severe events (admission to the ICU) or required invasive ventilation or death, 21.4% had admission to ICU, and mortality occurred in 28.6% of cases. In non-oncology patients, severe events were lower (4.7%) and mortality was 2.3%. On multivariate analysis, anticancer therapy within the past 2 weeks increased the risk of severe events (Hazard ratio [HR], 4.079, P = 0.037).
In comparison to the earlier study in which the rate of severe events was 39%, this study showed a higher severe event rate of 53.6%, possibly due to difference in the case definition of severe events in both studies.
| Covid-19 and Breast Cancer Challenges|| |
There are very limited data describing the effect of SARS-CoV-2 infection on patients with breast cancer. A detailed review of data published from China showed that only three of the affected 18 cancer patients had a breast primary. Out of the three patients, two were long-term survivors and both had undergone surgery followed by adjuvant chemotherapy.
There is a concern of disease recurrence and inferior outcomes if adjuvant therapy is delayed in breast cancer. In a retrospective analysis, patients with luminal B, triple-negative, HER2-positive tumors had inferior disease-free survival when the delay in adjuvant therapy was longer than 8 weeks. However, this did not influence outcomes in patients with the luminal A subtype.
The difficulties faced by cancer patients have further increased in this pandemic situation with the implementation of mitigation measures. These measures broadly affect the three domains of oncology care, i.e., patient care, education, and research, as shown in [Table 1]. With imposition of strict lockdown measures in India, patients are unable to travel to keep appointments or to carry out the required investigations and procure medications. With resources being diverted to the care of COVID-19 patients, routine appointments are being cancelled or postponed. And, this is happening not just for the outpatient department visits, but also for diagnostic procedures, investigations, and hospital admissions. A similar situation is seen with the supply chain of drugs and blood products. With the lockdown in place, there is an increasing scarcity of blood products. New donors are difficult to find as they have to travel to hospital for preparation, blood test, and the actual procedure while being at risk for exposure.
While most of the centers are dealing with this issue by delaying appointments, there is always a chance that such a delay might negatively affect the prognosis in cancer patients. In addition, with a continuously increasing number of cases of COVID-19, the duration of such a delay remains arbitrary, and there are no guidelines to help us decide what is the appropriate time for which the treatment of cancer can be delayed. In the Indian setting with an already-strained healthcare system, such a delay will increase the case load significantly in the post-pandemic time. This calls for careful planning and adapting according to the emerging scenario and continuation of cancer care whenever required, while simultaneously minimizing the risk of SARS-CoV-2 infection by effective infection prevention policies.
| Suggested Measures|| |
In clinical medicine, recommendations are usually evidence based and are backed by robust data. However, in the prevailing unprecedented circumstances, most of the recommendations are consensus based or of expert opinion. Various scientific bodies have given recommendations, most of them are broad suggestions for all malignancies.,,,, The recommendations and guidelines consider both disease-related and patient-related factors for appropriate management. Further, they stress on the fact that the final decision should be individualized according to the local prevailing circumstances. The American Society of Breast Surgeons has given guidelines specific to breast cancer. They have categorized breast cancer cases based on the urgency of requirement for therapy into priority groups A, B, and C. The highest priority is given to triple-negative breast cancer (TNBC) and HER2/neu clinical subtypes, who require adjuvant and neoadjuvant therapies.
Based on the above guidelines issued by various international authorities, the recommendations we suggest below for the Indian setting are expert opinions that we have started implementing at our center.,,,, The broad principles of these are elaborated in [Table 2]. The hospital should limit admissions and initiate telemedicine facilities. Multidisciplinary tumor board meets should be conducted through teleconferencing. This is to minimize the risk of contracting nosocomial SARS-CoV-2 infection. In patients on long-term follow-up, surveillance mammograms may be delayed until the pandemic settles. For patients who have TNBC and HER2/neu-positive breast cancers, neoadjuvant and adjuvant therapy should be initiated and continued, as depicted in [Table 3]. Dose-dense protocols are better avoided to decrease the risk of myelosuppression; also in addition, prophylactic growth factors are suggested. Considering the data support from abbreviated protocols of anti-HER2/neu therapies, adjuvant trastuzumab may be curtailed to 6 months, and may further be decreased to 9 weeks in T1/T2 node-negative disease.,, Weekly protocols should be changed to 3-weekly. For the luminal A subset, neoadjuvant hormonal therapy should be initiated and continued for 6–8 months with clinical response monitoring. Oral therapies should be preferred over infusional protocols, wherever feasible. CDK 4/6 inhibitors' use must be restricted because of the risk of neutropenia. In view of the concern of development of pneumonitis, immune checkpoint inhibitor drugs are better withheld.
|Table 2: Strategies to implement during coronavirus disease 2019 pandemic|
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|Table 3: Systemic therapy considerations for breast cancer during the COVID-19 pandemic|
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In view of the pandemic situation, elective surgeries are being delayed in order to divert the resources for SARS-CoV-2 management. In such circumstances, even patients with operable early-stage breast cancer should be started on neoadjuvant therapy. This may consist of cytotoxic chemotherapy ± targeted agents in TNBC/Her2 subset and hormonal agents in cases of hormone receptor-positive subset. In patients who have completed neoadjuvant therapy and are still awaiting surgery, targeted therapy with anti-HER2/neu agents and hormonal therapy may be continued. In the TNBC subset of patients, capecitabine may be initiated until surgery although there is no randomized trial to support this recommendation.
Based on limited clinical data, hydroxychloroquine sulfate (HCQS) has been granted off-label compassionate use indication by the United States Food and Drug Administration for the treatment of COVID-19. The Indian Council for Medical Research has approved the use of HCQS as prophylactic treatment in healthcare workers and close contacts. HCQS has been shown to increase viral clearance and also to accelerate clinical improvement., For confirmation, large randomized clinical trials are ongoing. With HCQS, there is a concern of QTc prolongation and the risk of torsade de pointes, especially when used along with azithromycin. Patients are encouraged to participate in clinical trials. HCQS should be cautiously used in patients with cancer and as a prophylaxis in healthcare workers and close contacts. Potential interaction with ribociclib/eribulin/anthracycline/trastuzumab should be considered. An electrocardiogram should be done prior to the use of HCQS in these patients.
Continued medical education and international and national conferences may be done by teleconferencing. While conducting research, the ethics committees should be approached for relaxation of norms and patient safety in these difficult times.
Finally, our healthcare system should be ready to manage the surge of breast cancer cases once the pandemic resolves.
| Conclusion|| |
The COVID-19 pandemic is an unprecedented emergency and poses huge challenges. Managing both COVID-19 and cancer is like navigating through an uncharted territory without a global positioning system in the absence of data. In such a scenario, the push should be toward curtailing the hospital visitations with telemedicine facilities, adopting chemotherapy protocols with minimal myelosuppression along with growth factor support, and using oral treatment regimens whenever feasible. Neoadjuvant therapies should be used even in early-stage breast cancer patients if surgeries are delayed. A note of caution is sounded regarding the use of HCQS along with QTc-prolonging agents. This needs adaptive strategies and effective infection control measures and prioritization of the treatment of malignancies with least immunosuppression and minimal hospital visitations.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]