Treating Breast Cancer During COVID-19: 'Indispensable'

A Discussion With Fatima F. Cardoso, MD, and Giuseppe Curigliano, MD, PhD

Fatima F. Cardoso, MD; Giuseppe Curigliano, MD, PhD


August 06, 2020

This discussion has been edited for length and clarity. Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Fatima F. Cardoso, MD

Fatima F. Cardoso, MD, director of the breast unit at Champalimaud Clinical Centre in Lisbon, Portugal; and Giuseppe Curigliano, MD, PhD, associate professor of oncology and hematology-oncology at the University of Milan, discuss the treatment protocols they have outlined, together with the editorial board of The Breast, in the recently published Recommendations for Triage, Prioritization and Treatment of Breast Cancer Patients During the COVID-19 Pandemic.

Cardoso: Before we get into the details of the manuscript, give us your personal view of the COVID-19 situation in Italy since it was one of the European countries that had the highest incidence of mortality. As an oncologist, what was your experience during the height of this pandemic?

Giuseppe Curigliano, MD, PhD

Curigliano: In Italy, we experienced the height of the pandemic from February 28 until the end of April. To date, we've had more than 35,000 people who died, and over 246,000 positive cases. Those with the highest risk factors have been the elderly and people with comorbidities, including cancer, and thoracic malignancies in particular.

After the lockdown on March 8, which lasted for 8 weeks, we started seeing a decrease in the number of COVID-19 patients. And up to now, we have fewer than 300 newly diagnosed COVID-19 cases per day and fewer than 10 deaths per day. So the situation is almost normal. We are not overwhelmed by COVID-19 patients, and I must confess that only the lockdown and social distancing measures helped to reduce the COVID-19 cases.

Cardoso: Thank you very much for sharing that. From my point of view, in Portugal, we had a different situation. I think we were lucky that we were able to learn from your experience, and we went into lockdown very quickly, so we never had as bad a situation as it was in Italy and Spain. To date, more than 1700 people have died, over 50,000 people have been infected, and more than 35,000 people have recovered. And at the moment, we have fewer than five deaths per day. I think it was important and effective that [assisted living] facilities for the elderly were closed to visitors very early on. That helped control the mortality rate among the elderly.

For us, the higher risk factors are the same: old age and comorbidities, particularly respiratory comorbidities. We don't have a lot of data about mortality in cancer patients because, fortunately, we did not have that many cancer patients who were infected, but it has been indicated as a risk factor. With respect to patients with cancer, I think it's mostly those who are on active treatment, not necessarily those who have a history of living with cancer for several years, that are at higher risk. That's important to note. Would you agree?

Curigliano: I completely agree with you that only cancer patients on active treatment, specifically chemotherapy, are at higher risk.

Cardoso: At the beginning of the pandemic, we had lots of patients contacting us who were on adjuvant endocrine therapy, asking if they had an increased risk of getting the virus. And I think it is safe to say that those who are on adjuvant endocrine therapy or follow-up care are at the same level of risk as the general population. Would you agree?

Curigliano: I completely agree that endocrine therapy is not a risk factor, and I have had no patients who were at higher risk of getting the virus while receiving endocrine therapy.

Cardoso: Exactly. I think that the main message we wanted to relay through the paper, as well as the ESMO guidelines, is that it is indispensable to continue to treat cancer during the pandemic, be it in the early or the metastatic setting. It seems that cancer — and today we're talking specifically about breast cancer — has a mortality rate that is much higher than the mortality rate of the COVID-19 infection. Therefore, it is important to keep practicing all the precautions that we're about to discuss from the paper, as well as the precautions you highlighted, such as social distancing, the use of masks, and washing and disinfecting hands. But we need to continue to treat our patients with cancer, and patients should not be afraid to seek out help.

We were very concerned about the fear that was taking over … regarding treatment for cancer during the pandemic.

Curigliano: Yes. I absolutely support your point of discussion because although we gave priority to COVID-19 patients, we missed a lot of cancer screenings, specifically in my country, and we expect to see an increase in cancer diagnoses going forward. It's quite important to understand, in case of a future pandemic scenario, how to allocate specific resources for cancer patients at any stage and for those patients who should undergo screening for breast cancer.

As we outlined in the paper, there are four scenarios of COVID-19 outbreak. In scenario one or two, where the virus is circulating but with isolated foci of COVID-19 transmissions, the objective is containment. What's important to note in these scenarios is that you can really take care of any patient without limiting access to the hospital. However, in scenarios three and four, where the transmission becomes widespread and the healthcare system tends to be overwhelmed, it is much more difficult to manage the best of care for cancer patients.

Fatima, can you explain what our aim was in writing this paper for The Breast?

Cardoso: We were very concerned about the fear that was taking over the governments, the health authorities, as well as the physicians and patients regarding treatment for cancer during the pandemic. And as you explained, there are different scenarios, including those scenarios during which it is correct and necessary to keep treating. And even in scenarios three and four, the majority of cancer treatments can and should continue.

Our goal was to help people prioritize, especially in view of the lack of resources in many countries because physicians and medical resources were being allocated to treat patients with COVID-19. Yet, we wanted to help patients have a good triage and also recommend which kinds of treatments should be continued and which could be postponed without hindering the outcomes.

We have done that for early breast cancer and for metastatic breast cancer, and I will ask you to summarize the recommendations for early breast cancer. You already mentioned the issue of screening and diagnoses and how that will impact the future, but can you now summarize the recommendations for the treatments, starting with surgery and then radiation and systemic therapy?

Curigliano: The unique characteristic of our paper is that we adapted the priority to the pandemic scenario. With regard to surgery in early breast cancer, we have scenarios one and two, in which the situation is almost normal, and then scenarios three and four. Within each scenario, we define what is urgent, high priority, medium priority, and low priority.

In scenarios one and two, of course, any type of treatment can be afforded by the surgeon. Hospitals are not overwhelmed by COVID-19 patients in these scenarios, so you can guarantee the best of care for all patients who have been newly diagnosed with breast cancer of any subtype.

In scenarios three and four, when there is a high risk for contamination in hospitals, an urgent surgical procedure is defined as any type of complication following surgery.

In high-priority situations, surgical treatment is recommended for locally advanced breast cancer not responding to primary systemic therapy, the surgical treatment of pregnant patients, and complicated locally advanced breast cancer not otherwise treated with any other therapy.

We define medium priority in pandemic scenarios three and four as patients with early isolated locoregional recurrence (within 24 hours of primary treatment); high-risk patients with no contraindications or with contraindications to primary systemic therapy, who are younger than age 40, or who have node-positive or biologically aggressive disease; and patients who were treated with primary systemic therapy and should have surgery following that therapy.

We defined low priority as patients with any type of ductal carcinoma in situ, including small size or high-grade tumors; those with postmenopausal luminal A cancer that can be treated with neoadjuvant endocrine therapy; premenopausal patients with a stage I invasive cancer; and finally, ductal carcinoma in situ with high-grade ER-negative extensive disease or palpable mass.

Regarding radiation therapy, in scenarios three and four, urgent priority is given to cases of acute spinal cord compression. Continuation of already-started radiation therapy and palliative treatments are high priority. Postoperative radiation therapy for high-risk patients and patients on treatment with symptoms are considered medium priority. Postoperative radiation therapy for intermediate-risk patients is low priority.

When considering early breast cancer, systemic therapy is preferred, owing to established benefits, and this is the case for any condition in which you may derive a benefit in terms of overall survival from any neoadjuvant or adjuvant chemotherapy treatment. What's considered an urgent situation, for instance, is a patient with locally advanced HER2-positive breast cancer who can benefit from dual blockade and chemotherapy. This is a condition where you should start chemotherapy plus pertuzumab and trastuzumab. The same is recommended for treatment of triple-negative breast cancer. In the course of therapy, the use of growth factors should be considered.

Endocrine therapy to delay surgery in patients with ER-positive disease and select patients with HER2-positive breast cancer who will not receive a neoadjuvant treatment is defined as high priority in all four scenarios.

Under medium priority, all scenarios, we include any treatment for postmenopausal women with stage I intermediate-grade tumors with a MammaPrint test or Oncotype DX scores showing a low risk for metastasis. In scenarios three and four, the continuation of treatment in the context of a clinical trial is also considered medium priority. Any follow-up in imaging, restaging studies, and similar testing that requires access to hospitals is low priority in all scenarios.

So now, would you explain what is defined as urgent, high priority, medium priority, and low priority in the context of metastatic breast cancer treatment?

Cardoso: We just discussed the importance of prioritizing treatment for early breast cancer. This is also the case, perhaps more so, for patients with metastatic breast cancer. If we stop treatment for metastatic breast cancer, death will occur quickly; therefore, almost every treatment is either high priority or, at the least, medium priority.

Under the urgent designation, we included patients with visceral crisis in whom immediate treatment is required. This is the case for all four scenarios. Treatment with anti-HER2 agents is recommended for patients with HER2-positive advanced disease. As far as we know, anti-HER2 agents don't have any contraindications during this or any other pandemic and are very efficacious. Therefore, this treatment is considered urgent.

We recommend as high priority, in all four scenarios, that patients with metastatic breast cancer who need chemotherapy should get started, but that preference should be given to oral treatments. In fact, our metastatic breast cancer guidelines already recommend this even outside the pandemic circumstances because oral treatments may help reduce the need for visits to the hospital. Dose reductions may also be considered to minimize side effects, always keeping in mind that efficacy is crucial, as well as maintaining treatment with good quality of life. We also highlight that chemotherapy schedules may be adjusted to avoid too many hospital visits and, when appropriate, we recommend the use of growth factors to reduce side effects causing immunosuppression.

Moving to the discussion of endocrine therapy, we already mentioned that there is no contraindication, therefore the treatment should not be delayed or stopped, as the case may be. The agents we are now using combined with endocrine therapy, such as the CDK4/6 inhibitors or the PI3K inhibitors, have some side effects. For instance, CDK4/6 inhibitors are associated with neutropenia. However, we consider this on a case-by-case basis, and we must balance the benefits and the risks. These agents have shown an overall survival benefit, so it's important to make the pros and cons clear to patients. For example, in our practices, we favor the continued use of these agents, but we ask patients receiving this therapy to stay at home or avoid public places so that they're more protected from the risk for infection. Although it's worth pointing out that neutropenia as a side effect of CDK4/6 inhibitors has not been associated with high risk for severe infection as has chemotherapy-induced neutropenia, for example. Also consider that CDK4/6 inhibitors can be used in first- or second-line treatment; therefore, the use of these agents may be postponed in the second-line setting. We consider treatments with these agents as high priority in scenarios one and two.

PI3K inhibitors are much more toxic, so they usually require several visits to the hospital because of side effects, and they are also more difficult to tolerate. We consider use of these agents as medium priority in all four scenarios. Again, this is based on a case-by-case evaluation of the potential benefits and risks of adding this treatment to a patient's regimen.

Participating in a clinical trial, especially for patients with metastatic cancer, is sometimes the most appropriate available treatment option. Therefore, particularly in scenarios one and two, we find that continuing or being enrolled in a clinical trial is a high priority. For scenarios three and four, we place clinical trial treatment as medium priority; again, always based on a case-by-case evaluation. The only thing we consider low priority for patients with metastatic breast cancer is routine follow-up imaging or restaging if the patient is asymptomatic and a proper follow-up can be done with clinical and blood test results. In a nutshell, these are the recommendations for metastatic disease.

Would you like to add anything to what we have already discussed?

Curigliano: You presented a clear review of the treatment priorities in the metastatic breast cancer setting. Of course, patients with metastatic breast cancer may have lung disease. They may be on chemotherapy, so we need to intensify the monitoring.

Cardoso: Yes, and also monitor patients closely when they're using agents that are linked to a risk for pneumonitis or interstitial lung disease, such as the mTOR or the PI3K inhibitors, for example, or the CDK4/6 inhibitors discussed. The same is true for the side effects associated with the new agent trastuzumab deruxtecan.

And we have not mentioned the use of bone-modulating agents, again, which should be determined on a case-by-case basis. For patients who have multiple bone metastases, the use of these agents is appropriate. However, there are several ways of prescribing them, and we may want to avoid IV administration during the pandemic

Would you like to share any final thoughts?

Curigliano: In our experience in Italy, I would like to highlight that the most important risk factors were older age, comorbidities, and receiving chemotherapy for active cancers. In the event of a new wave of pandemic transmission, I recommend that we remain aware of and take special care of these patients, protect them, and practice social distancing early on as you did in Portugal.

Cardoso: For my part, I'd like to add that if we have a second wave, we should take into account all that we have learned. Particularly, that we do not delay the diagnosis and treatment of cancer, breast cancer or any other cancer. We are already seeing an increase in locally advanced disease and, in some cases, metastatic disease at diagnosis. We want to avoid that.

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