Keywords:
Breast Neoplasms - Pandemics - Coronavirus
INTRODUCTION
The coronavirus disease 2019 (COVID-19) pandemic has challenged the medical community,
including those in the field of clinical oncology, which has always required priority
in the diagnosis and treatment of patients.
The Breast Tumors Committee of the Brazilian Society of Clinical Oncology (SBOC) brought
to light some relevant decisions to guide medical oncologists during this pandemic,
pointing out that there is a scarcity of scientific data related to this scenario.
The following recommendations for systemic treatment and surgery decisions are based
on biological subtypes of breast cancer.
RECOMMENDATIONS ON BREAST CANCER TREATMENT ACCORDING TO BIOLOGICAL SUBTYPES[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
RECOMMENDATIONS ON BREAST CANCER TREATMENT ACCORDING TO BIOLOGICAL SUBTYPES[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
LUMINAL A INVASIVE BREAST CANCER
These recommendations include luminal A-type cancers (immunohistochemistry profile
of high expression of estrogen receptor [ER] and progesterone receptor [PR], negative
human epidermal growth factor receptor 2 [HER2], and low Ki-67) and luminal A breast
cancers assessed by genomic tests.
Clinical Stage I-II disease
-
Treat with neoadjuvant endocrine therapy (ET).
-
Perform surgery after 3-4 months or when appropriate if responding to ET (Stage I
and II luminal tumors are usually indolent and respond very well to ET).
-
Surgery may be postponed with apparently no impact on survival.[9]
[10]
[11]
Clinical stage III disease
-
Discuss neoadjuvant chemotherapy (NACT) or neoadjuvant ET.
-
Perform surgery after 4-6 months of neoadjuvant treatment as appropriate (In stage
III luminal breast cancer, neoadjuvant ET is a reasonable approach with significantly
improved surgical outcomes.[12]
LUMINAL B HER2-NEGATIVE INVASIVE BREAST CANCER
This includes luminal B-type cancers (ER-positive, HER2-negative and one of the following:
high Ki-67 or low/negative PR by immunohistochemistry) and luminal B breast cancers
assessed by genomic tests.
Clinical Stage I-II disease
Clinical stage III disease
-
Administer NACT
-
Perform surgery after 4-6 months of neoadjuvant treatment as appropriate (Oncotype
DX™ can be performed in the core-biopsy prior to surgery, and can guide the therapeutic
decision between the choice of neoadjuvant ET or NACT, or whether surgery should be
prioritized[13] ).
TRIPLE NEGATIVE BREAST CANCER (TN)
This includes breast cancers that are ER-negative, PR-negative, and HER2- negative.
cT1a, cN0
cT1b, cN0
-
Discuss with the multidisciplinary team: NACT is advised for invasive TN disease >
6 mm; otherwise, prompt surgical intervention is recommended (at the earliest favorable
moment, considering risks versus benefits).
= cT1c, N0 or N+
HER2-POSITIVE BREAST CANCER
This includes invasive breast tumors that are:
-
- ER-positive, HER2 over-expressed or amplified, any Ki-67 and any PR or,
-
- HER2 over-expressed or amplified, ER-negative and PR-negative
cT1a, cN0
cT1b, N0
-
Discuss with the multidisciplinary team: NACT with anti-HER2 if invasive HER2 positive
breast cancer > 6 mm (given that in pT1b lesions, adjuvant CT + anti-HER2 blockage
is indicated).
-
If NACT is not considered, recommend surgery as soon as possible (if initial surgery
is required, select the earliest option available, considering risks versus benefits.
=cT1c, N0 or any N+
RECOMMENDATIONS ON CHEMOTHERAPY SCHEMES[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
RECOMMENDATIONS ON CHEMOTHERAPY SCHEMES[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
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There are no CT schemes of choice during the pandemic period, but it may be suitable
to favor exceptional schemes every 14 days or 21 days instead of weekly schemes that
will result in multiple visits and consequently increased risk of infectious exposure.
If possible, medical appointments should occur on the same day as the chemotherapy
infusion, to reduce the number of patient visits to the hospital or clinic.
-
Schemes with lower risk for gastrointestinal toxicity or febrile neutropenia and consequent
lower risk of hospitalization are favored in order to avoid health system overload
and risk of individual exposure.
-
In cases where CT indications are borderline, a genomic test like Oncotype DX? or
MammaprintT? is suggested to increase the chance of avoiding unnecessary CT during
the pandemic. In the absence of genomic tests, we suggest using the MINDACT clinical
risk criteria to avoid unnecessary CT. In exceptional circumstances, Oncotype DX™
can be performed during the core- biopsy in luminal B-type tumors (see above).
-
In cases where colony-stimulating factors are required, the pegylated form should
be used, given that it is administered in a single dose. If the pegylated formula
is unavailable, offer filgrastim and guide patients on how to store it and how to
perform multiple shots at home.
RECOMMENDATIONS ON ANTI-HER2 THERAPY[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
RECOMMENDATIONS ON ANTI-HER2 THERAPY[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
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Always favor trastuzumab and pertuzumab schemes every 21 days. Consider exchanging
intravenous (IV) for subcutaneous (SC) trastuzumab to reduce the time spent at the
chemotherapy unit.
-
In selected cases where weekly paclitaxel for 12 weeks with trastuzumab for 1 year
(APT scheme)[14] is indicated, consider switching to adjuvant trastuzumab emtansine (T-DM1) every
three weeks, despite there being no label indication for T-DM1 in this scenario[15]. This may reduce patient exposure compared to the APT scheme.
-
The indication for adjuvant T-DM1 in residual disease after NACT remains valid[16] and routine hepatic tests and platelet blood counts can be spaced and/or evaluated
remotely by telemedicine, thereby reducing the number of visits, according to the
recent regulations of the Brazilian Federal Council of Medicine.
RECOMMENDATIONS ON ADJUVANT ENDOCRINE THERAPY[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
RECOMMENDATIONS ON ADJUVANT ENDOCRINE THERAPY[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
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ET must continue to be carried out during the pandemic period using either tamoxifen
or aromatase inhibitors. Medical appointments may be postponed and patient questions
can be handled by tele-medicine.
-
Patients at high risk for recurrent disease, who have indicators of suppression of
ovarian function (SOF) or who are already receiving monthly LHRH agonist therapy,
can start or switch to schemes that are applied every 12 weeks, thereby reducing the
number of patient visits to the clinic. When tamoxifen is combined with SOF, the later
may be temporarily suspended.
RECOMMENDATIONS ON BREAST SURGERY[2]
[3]
[5]
[8]
[17]
[18]
RECOMMENDATIONS ON BREAST SURGERY[2]
[3]
[5]
[8]
[17]
[18]
CONSIDER DELAYING SURGERY WITHOUT IMPACT ON PROGNOSIS IN THE FOLLOWING CASES:
-
Benign nodules
-
Delayed breast reconstruction
-
Mastectomies (in general and in cases of metastatic cancer) and hygienic surgery,
except in rare cases of bleeding refractory to radiotherapy
In the case of pathological fractures, a multidisciplinary discussion of the risks
and benefits of surgery in a pandemic environment should take place. The decision
must take into account the potential for functional recovery with good quality of
life.
CONSIDER DELAYING SURGERY WITH VERY MILD IMPACT ON PROGNOSIS IN THE FOLLOWING CASES:
-
Prophylactic surgeries (patients with pathogenic genetic variants)
-
Resections of atypical findings and/or precursor lesions (atypical ductal hyperplasia;
atypical lobular hyperplasia; lobular carcinoma in situ)
CASES OF IN-SITU DUCTAL CARCINOMA (DCIS) CASES WITH NO SUSPECTED ASSOCIATED INVASIVE
DISEASE:
The cases of low risk DCIS are defined by the criteria of LORIS:
-
-Age > 45 years;
-
-Low grade DCIS with biopsy;
-
-Microcalcifications in the image as the only finding;
-
-Extension < 5 cm;
-
-No palpable lesions; or
-
-Paget papillary discharge.
-
In cases that are hormone receptor (HR)-positive, consider initial pharmaco- prophylaxis.
-
In cases that are HR-negative, pharmacoprophylaxis is not indicated (consider the
statement below).
-
Consider postponing surgery for 3-4 months or performing surgery once it is deemed
safe.
CASES OF DCIS WITH SUSPECTED ASSOCIATED INVASIVE DISEASE:
High-risk DCIS is defined as extensive/ palpable lesions accompanied by the possibility
of invasive disease, or which do not meet the above criteria for low- risk DCIS.
-
In cases that are HR-positive, consider initial pharmaco-prophylaxis.
-
In cases that are HR-negative, there is no indication for pharmaco-prophylaxis (consider
the statement below)
-
Consider surgery promptly.
SURGERY AFTER NEOADJUVANT TREATMENT:
-
Consider delaying surgery after neoadjuvant treatment as long as possible (technical
limit of 4-8 weeks or until improvement of logistics and adequate safety conditions).
-
If NACT is concluded and the disease is HRpositive, consider ET as a bridging measure
with or without SOF until surgery may be safely performed (it is not recommended to
increase the number of NACT cycles).
-
In cases of HER2-positive disease, consider maintaining double-blockade if available
(or at least trastuzumab) for a few additional doses after completion of NACT, based
on the previous argument.
-
In cases of TN disease, prompt surgery is recommended, considering the risk vs benefit,
4-6 weeks after NACT. In exceptional cases where surgery is not available within a
reasonable period of time, consider neoadjuvant radiotherapy (RT).
SCENARIOS IN WHICH SURGERY SHOULD BE PROMPTLY CONSIDERED:
RECOMMENDATIONS ON RADIOTHERAPY (RT)[1]
[2]
[4]
[5]
[18]
RECOMMENDATIONS ON RADIOTHERAPY (RT)[1]
[2]
[4]
[5]
[18]
-
For patients with stages I and II low-risk luminal tumors where adjuvant CT is not
indicated and who are candidates for adjuvant ET, consider delaying the start of RT
to 3-6 months from the date of surgery. Additionally, consider hypo- fractionation
(40 Gy in 15 fractions in 3 weeks) or the lowest possible number of treatment days.
-
Omit RT in elderly patients (> 65-70 years) with low-risk disease and negative axilla
or in younger patients with low-risk disease and negative axilla with serious co-morbidities.
-
Patients with DCIS can also avoid adjuvant radiotherapy after assessment of risk versus
benefit.
-
Patients with negative axilla who do not require a boost can be candidates for hyper-fractioning
(28-30 Gy/single weekly dose in 5 weeks or 26 Gy in 5 daily sessions in one week)
if the technique is available.
-
Hypo-fractionation (40 Gy/15 days/3 weeks) can be used in all cases of breast, chest
wall and drainage chains radiation therapy.
-
For patients with luminal tumors who have newly undergone surgery after NACT and who
are candidates for adjuvant ET, RT can be delayed for up to 3 months after surgery.
-
For patients with stages I and II HER2-positive tumors who have undergone surgery
after NACT where follow-up with adjuvant treatment and anti-HER2 blockade is indicated,
RT can be delayed for up to 3 months after the end of chemotherapy.
-
For patients with stage III HER2-positive tumors who have undergone surgery after
NACT and for whom adjuvant treatment and anti-HER2 blockade are indicated, RT can
be delayed for up to 3 months after the end of chemotherapy, especially when a pathological
complete response (pCR) is achieved. Consider earlier RT in cases where pCR is not
achieved.
-
For patients with TN tumors after adjuvant CT, RT can be postponed for 3 months after
completion of CT
-
For patients with TN tumors, when there is residual disease and indication of adjuvant
capecitabine after NACT, RT may be considered immediately following completion of
adjuvant CT, due to the high risk of recurrence.
-
For patients with TN tumors who have achieved pCR after NACT, RT can be delayed for
up to 2-3 months.
-
In cases of metastatic breast cancer, consider bone antialgic single dose radiotherapy
if possible; for other indications of RT in metastatic sites (e.g. whole brain, antihemorrhagic),
consider the minimum number of fractions possible.
RECOMMENDATIONS OF FOLLOW-UP AND ROUTINE EXAMS[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
RECOMMENDATIONS OF FOLLOW-UP AND ROUTINE EXAMS[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
-
To avoid unnecessary medical office visits, some follow-up exams should be postponed
until the end of the pandemic period, without increasing patient risks or influencing
prognosis; consider tele-medicine if available.
-
Screening tests for patients with suspected metastatic disease and biopsies in new
cases or in suspected cases of recurrence should be performed when feasible, still
aiming to avoid multiple visits and unnecessary patient exposure to the risk of infection
with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
-
Imaging tests to assess the response of metastatic disease in patients with clear
clinical benefits and oligo/asymptomatic disease may be postponed at the clinician's
discretion.
RECOMMENDATIONS ON LONG-TERM CENTRAL VENOUS CATHETERS[1]
[2]
[4]
[5]
[18]
RECOMMENDATIONS ON LONG-TERM CENTRAL VENOUS CATHETERS[1]
[2]
[4]
[5]
[18]
-
Consider cleaning long-term central venous catheters every 12 weeks.
-
Withdrawal of these catheters should be postponed until the pandemic period has passed.
-
Catheter placement should be avoided if possible, after discussing the risks and benefits
according to the treatment protocol.
RECOMMENDATIONS ON INJECTABLE BISPHOSPHONATES AND DENOSUMAB[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
RECOMMENDATIONS ON INJECTABLE BISPHOSPHONATES AND DENOSUMAB[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
-
Consider postponing these treatments during the pandemic period if the indication
is for adjuvant use or prevention and / or treatment of osteoporosis.
-
In the case of metastatic disease, delay infusion of zoledronic acid to every 12 weeks;
if zoledronic acid is used monthly, consider switching to every 12 weeks. Space monthly
denosumab as needed if the patient has oligo/asymptomatic, low-volume disease without
high risk of skeletal events, and no hypercalcemia.
RECOMMENDATIONS ON GENETIC COUNSELING[1]
[2]
[4]
[5]
[18]
RECOMMENDATIONS ON GENETIC COUNSELING[1]
[2]
[4]
[5]
[18]
-
Consider postponing genetic counselling if there is no clear impact on medical practice
for the next 3-6 months; consider tele-medicine if there is an urgent need for an
appointment.
-
Consider performing genetic testing for the evaluation of pathogenic variants of BRCA
1 and BRCA 2 for possible indication of platinum and/ or olaparib; the tests should
be performed using a simple salivary home-based test kit, if available, to avoid unnecessary
visits to the laboratory.
RECOMMENDATIONS FOR METASTATIC DISEASE[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
RECOMMENDATIONS FOR METASTATIC DISEASE[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
-
Do not stop treatments that provide a clear clinical benefit such as chemotherapy,
endocrine treatment, immunotherapy or biological anti-HER2 treatments. If feasible,
consider spacing medical visits and exams. Use tele- medicine whenever possible.
-
Whenever possible, choose treatments with fewer toxicities to minimize visits to the
emergency department and facilitate fewer clinical appointments and evaluations.
-
Whenever possible, prescribe fewer cycles of chemotherapy, concluding CT after 4-6
cycles or upon improved response, utilizing anti-HER2 therapy, bevacizumab, atezolizumab
or single ET (in HR-positive tumors) as maintenance therapy, thus reducing the duration
of exposure to immunosuppressive chemotherapy and steroid treatments.
-
Preferentially prescribe monotherapy in cases of palliative CT; in HR-positive disease,
consider single endocrine treatment, avoiding initiation of treatments with increased
risk of pulmonary toxicity such as everolimus. In cases where alpelisib is used, perform
an endocrinologic assessment to better control blood glucose in order to reduce the
risk of grade III hyperglycemia (and therefore the risk of hospitalization). Patients
using everolimus or alpelisib with adequate responses and good tolerance must be carefully
evaluated for continuation of these treatments.
-
Cyclin inhibitors can be started and continued in combination with ET, due to the
robust increase in overall survival associated with these combinations. Patients must
be closely monitored for hematological, gastrointestinal and other side effects and
exams can be performed and shared with the medical team electronically by tele-medicine.
-
Patients with advanced disease and life expectancy less than 3 months should be referred
to palliative care, avoiding futile treatments that overwhelm the health system with
toxicities, unnecessary hospitalizations and possible mechanical ventilators aimed
at use in terminally ill patients.
-
Delays in cycles, dates of treatment, and routine visits in the context of the pandemic
and in the context of a non-curative treatment are perfectly acceptable.
-
Patients with good performance status, irrespective of age, should receive appropriate
cancer treatment notwithstanding the pandemic. In most cases it will not be possible
to delay the start of treatment for 3-4 months, therefore, a shared decision should
be proposed, respecting the patient's opinion and considering limitations and difficulties
in the access and availability of emergency services.
RECOMMENDATIONS FOR PATIENTS WITH FEVER, RESPIRATORY SYMPTOMS (COUGH, CORYZA, DIFFICULTY
IN BREATHING) OR WITH SUSPECTED OR CONFIRMED COVID-19 DIAGNOSIS[6]
RECOMMENDATIONS FOR PATIENTS WITH FEVER, RESPIRATORY SYMPTOMS (COUGH, CORYZA, DIFFICULTY
IN BREATHING) OR WITH SUSPECTED OR CONFIRMED COVID-19 DIAGNOSIS[6]
-
Advise patients to always contact their medical team. If there is no shortness of
breath, they are advised to stay at home in social isolation for 14 days unless the
medical team can provide a COVID-19 test, and to maintain contact with the doctor
by tele-medicine throughout this period.
-
Cases with warning symptoms (shortness of breath, respiratory distress, O2 saturation
<95%, worsening in the clinical conditions of pre-existing disease, severe abdominal
pain) should seek emergency service.
-
Patients with fever and respiratory symptoms should discontinue any systemic cancer
treatments until symptoms are resolved.
FINAL CONSIDERATIONS:
These are general recommendations. All cases should be discussed on an individual
basis with the multidisciplinary team and shared decisions between the medical team
and the patient must be guided. It is strongly recommended to maintain multidisciplinary
meetings through web conferences for the optimal management of all cases. It is also
recommended that these recommendations be adjusted according to the reality of each
service (private or public) and according to the epidemiological issues COVID19 presents
in each area. Revised recommendations may arise at any time.
Bibliographical Record
Gilberto Luiz da Silva Amorim, Daniele Xavier Assad, Bruno Lemos Ferrari, Daniela
Dornelles Rosa, Bruno Pacheco Pereira, Renan Orsati Clara, Clarissa Maria de Cerqueira
Mathias. Breast oncology and the COVID-19 pandemic: Recommendations from the Brazilian
Society of Clinical Oncology (SBOC). Brazilian Journal of Oncology 2020; 16: e-20190024.
DOI: 10.5935/2526-8732.20190024
