The Breast 52 (2020) 8e16

Contents lists available at ScienceDirect

The Breast
journal homepage: www.elsevier.com/brst

Original article

Recommendations for triage, prioritization and treatment of breast

cancer patients during the COVID-19 pandemic
Giuseppe Curigliano a, b, 1, *, Maria Joao Cardoso c, d, Philip Poortmans e, f, Oreste Gentilini g,
Gabriella Pravettoni a, b, Ketti Mazzocco a, b, Nehmat Houssami h, Olivia Pagani i,
Elzbieta Senkus j, Fatima Cardoso c, on behalf of the editorial board of The Breast
a
Istituto Europeo di Oncologia, IRCCS, Department of Early Drug Development, Italy
b
University of Milano, Milano, Italy
c
Breast Unit, Champalimaud Clinical Centre/Champalimaud Foundation, Portugal
d
Nova Medical School, Lisbon, Portugal
e
Iridium Kankernetwerk, Department of Radiation Oncology, Wilrijk-Antwerp, Belgium
f
University of Antwerp, Faculty of Medicine and Health Sciences, Wilrijk-Antwerp, Belgium
g
Breast Surgery, San Raffaele University and Research Hospital, Milano, Italy
h
Faculty of Medicine and Health, Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia
i
Service Interdisciplinaire de Canc
erologie, Hopital Riviera-Chablais, Rennaz, Vaud, Geneva University Hospitals, Swiss Group for Clinical Cancer Research
(SAKK), Switzerland
j
Medical University of Gdansk, Gdansk, Poland

a r t i c l e i n f o a b s t r a c t

Article history: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) associated disease (COVID-19)
Received 6 April 2020 outbreak seriously challenges globally all health care systems and professionals. Expert projections es-
Received in revised form timate that despite social distancing and lockdown being practiced, we have yet to feel the full impact of
9 April 2020
COVID-19. In this manuscript we provide guidance to prepare for the impact of COVID-19 pandemic on
Accepted 9 April 2020
Available online 16 April 2020
breast cancer patients and advise on how to triage, prioritize and organize diagnostic procedures, sur-
gical, radiation and medical treatments.
© 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction mild symptoms, about a quarter of patients develop severe symp-

toms and 5% will have critical symptoms. The clinical manifesta-
The outbreak of the severe acute respiratory syndrome coro- tions, as well as case fatality rates have been higher in the elderly,
navirus 2 (SARS-CoV-2) associated disease (COVID-19) has rapidly those with comorbidities such as respiratory and cardiovascular
escalated to pandemic proportions. By the beginning of April 2020, disease, males and smokers [2]. There is currently no approved nor
over 1,000,000 cases of confirmed infections and over 66,000 proven effective treatment or vaccine available for COVID-19, but
deaths from COVID-19 were reported worldwide [www. there are several ongoing trials of potential therapies.
worldometers.info/coronavirus]. The most common symptoms of COVID-19 has led to a severe overloading of hospital systems in
COVID-19 are new onset of a continuous cough and/or temperature most affected regions and countries [3]. Healthcare resources

37.8  C [1]. Ageusia and anosmia are also frequent symptoms at (human as well as material) have been rearranged to manage the
the early phase of diagnosis [1]. While most patients have no or influx of a large number of patients requiring intensive monitoring,
artificial ventilation, and in selected cases extracorporeal mem-
brane oxygenation [4]. Even in countries where COVID19 has not
attained very high incidence rates, containment measures are
* Corresponding author. Division of Early Drug Development for Innovative
Therapies, European Institute of Oncology IRCCS, University of Milan, Department recommended and are being implemented, to prevent infections
of Oncology and Haemato-Oncology, Via Giuseppe Ripamonti n. 435, 20141, Milan, both of patients and healthcare professionals. The response to this
Italy. pandemic has led to a sudden disruption of routine medical care,
E-mail address: [email protected] (G. Curigliano).
1 including the treatment of cancer patients, an especially vulnerable
All authors equally contributed to the design, manuscript writing, editing and
final approval of the current manuscript. population, whose outcomes are dependent on timely and high-

https://doi.org/10.1016/j.breast.2020.04.006
0960-9776/© 2020 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/
).
 G. Curigliano et al. / The Breast 52 (2020) 8e16 9

quality multidisciplinary interventions [5]. Travel restrictions have

made it difficult for some cancer patients to reach the hospital and
the fear of infection while visiting the hospital has caused many
others to cancel their appointments. Staffing gaps within the
oncology departments have arisen as a result of redeployment and
sequestering of medical and supporting staff to other areas of
critical need e such as respiratory units, emergency departments,
and intensive care units (ICUs), as well as self-isolation or quaran-
tine of staff members with suspicious symptoms and/or positive
SARS-CoV-2 test [6]. Consequently, many routine visits to the
outpatient clinics have been either replaced by telephone/video
consultation or deferred.
Independently of whether in a general hospital or in an
oncology facility, measures need to be put in place to protect pa-
tients and health professionals, and to create a safe circuit to treat
or transfer (according to country/regional directives) SARS-CoV-2
infected patients with cancer. These actions have also a strong
impact on available resources and routine processes that need to be
considered to avoid system disruption.
As breast cancer specialists, our main goal is to take care of
breast cancer patients within a multidisciplinary environment, able Fig. 1. PDCA is an iterative four-step management method aimed at continuous
to provide high level treatment within the shortest period of time improvement of processes [7].

and according to established quality indicators. However, the cur-

rent extraordinary worldwide situation requires an urgent re-
parameters and be balanced not only for the safety of individual
organization and adapted allocation of healthcare resources, staff
patients but also for the community. The PDCA
as well as infrastructures without compromising patients’
(planedoecheckeact or planedoecheckeadjust) approach is
outcomes.
aimed at continuously following, monitoring and improving the
The aim of the present recommendations is to provide guide-
organization based on the obtained results in every single hospital
lines, including selection criteria to service provision and prioriti-
and/or department (Fig. 1).
zation of treatments, according to the pandemic scenario in each
Therefore, the following proposals must be interpreted as
country/region (Table 1), for breast cancer patients care during this
extraordinary, limited to the duration of the contingent pandemic
critical moment when benefits and risks are influenced by a serious
situation, and should be adapted to national/regional circum-
external health threat. This necessitates that all current medical
stances taking into account existing public health regulations. We
decisions must be carefully weighed taking into account unusual

Table 1
Scenarios to describe progression of COVID-19 outbreaks - according to ECDC.
10 G. Curigliano et al. / The Breast 52 (2020) 8e16

highlight that these considerations do not overcome the individual 1.3. Screening and diagnosis (Table 2)
physician judgment or available treatment guidelines but represent
an expert-opinion-based guidance for optimal allocation of re- 1. Due to the foreseeable reduction of resources and to ensure the
sources during an unprecedented critical period, drawing on cur- safety of patients and staff, population mammographic
rent knowledge in a rapidly emerging and evolving situation. screening should be suspended until the pandemic has subsided
[4,5,11,12].
2. Diagnostic procedures in symptomatic patients should be
scheduled according to local availability and resources. How-
1.1. Proposed risk stratifications [8,9]
ever, all efforts should be made to avoid delayed diagnosis in
those with suspicious symptoms or clinical or imaging findings
I) Breast cancer patients recently suspected or recently
[BIRADS 5 (high priority) or BIRADS 4 (medium priority)] and its
diagnosed
potential impact on cancer outcomes [4,5,11,12].
II) Breast cancer patients on active treatment (i.e. chemo-
therapy, immunotherapy, anti-HER2 therapy, endocrine
therapy with or without targeted therapies)
III) Breast cancer patients in follow-up (non-active treatment) or 1.4. Locoregional treatment in early breast cancer (EBC)
on adjuvant endocrine therapy alone
1.4.1. Surgery versus primary systemic treatment (Table 3)
Supplementary risk factors: age over 60/pre-existing cardio- Under normal circumstances, primary systemic therapy (PST) is
vascular disease/pre-existing respiratory disease/smokers/males. increasingly used and preferred over upfront surgery, not only for
locally advanced disease but also in the EBC setting, both within
and outside clinical trials. This is due to the established benefits of
this approach in terms of surgical de-escalation and more recently
1.2. General recommendations (Table 2)
to optimize further adjuvant treatments. PST includes both neo-
adjuvant/primary chemotherapy ± anti-HER2 therapy (NAC) and
1. Patients should be informed and guided to follow all measures
neo-adjuvant/primary endocrine therapy (PET).
of social distancing and wearing personal protective equipment
During the COVID-19 pandemic, PST indications in EBC patients
(i.e. mask) when travelling to the hospital, always in compliance
may be temporarily reconsidered taking into account the avail-
with each country public health regulations.
ability of facilities and healthcare resources, the number of required
2. Early identification of symptoms suspicious of SARS-CoV-2
hospital visits and the risks of compromising the immune system
infection is crucial, as well as of symptoms or adverse events
associated with different type of treatments [9,12e14]. The situa-
caused by the malignancy or antitumor treatments. This pre-
tion might widely vary according to different countries but also in
screening can be done by phone before each appointment at
different cities and different hospitals. Therefore, it is even more
the hospital and/or at the entry of the hospital. Body tempera-
critical that indications for treatment are taken in a multidisci-
ture should be measured at the entry of the hospital. Patients
plinary setting, in light of what is deemed to be the best option for
with symptoms suspicious of SARS-CoV-2 infection, should be
each patient in that specific time and place. A crucial balance is
tested and managed in a COVID-19 hospital or in the COVID-19-
needed between maintaining a high quality of breast cancer care,
dedicated departments/areas of the cancer center.
not jeopardizing cancer outcomes, and minimising both the risks of
3. Patients who need to be hospitalized for cancer treatment
infection by SARS-CoV-2 and the risks of complications of anti-
should be treated in COVID-19-free hospitals or COVID-19-free
cancer treatments. The decision between primary surgery or PST
departments/areas of the hospital and be, as much as possible,
should also take into account the pandemic scenario (Table 1) in
shielded from potential SARS-CoV-2 infection, with a dedicated
each center (i.e. early stages vs mitigation phase vs recovery phase).
diagnostic and therapeutic internal pathway.
For instance, some patients with EBC who under normal circum-
4. No visits should be allowed in the inpatient facilities and no
stances would receive PST might be treated with primary surgery
accompanying care giver should enter the hospital with the
especially when a limited procedure is feasible in an outpatient
patient for appointments or treatments.
setting. In contrast, some patients who, under normal circum-
5. Staff should be organized by shifts, limiting the number of
stances, could be treated with primary surgery, such as post-
people working simultaneously to the minimum required.
menopausal women with limited luminal A/B disease, might be
6. The multidisciplinary tumour boards (MDM) should be
treated with primary endocrine therapy in order to delay invasive
continued but performed via web meetings or restricted to one
procedures and hospitalization.
element of each discipline of the core team [10]. All decisions of
the MDM should continue to be discussed with the patient and
the final decision must account for the patients’ preferences. 1.5. Surgery (Table 3)
7. Due to different availability of tests and different public health
measures taken in each country, we recommend that testing At this point in time, when surgery is indicated, preference
guidelines of the national health authorities are followed. If tests should be given to the most effective minimal surgical procedure
are available, patients should be tested for SARS-CoV-2 before with the fastest recovery time, that lower risks for the individual
surgery or any invasive procedure and before initiating immu- patient and reduce the need of healthcare resources. These general
nosuppressive therapies, independently of symptoms. If posi- recommendations should be applied even in countries where the
tive, the procedure and/or treatment should be postponed and outbreak has not yet dramatically affected the health system and
resumed only after the patient is considered recovered. How- the surgical activity is still maintained with a reduction that is less
ever, it is important to realize that even with this approach, than half the usual production [13,15e17].
some cases will be missed in view of the false negative rate of
the PCR test on pharyngeal swabs. 1. Defer all benign, cosmetic, and risk-reducing procedures.
2. Offer outpatient surgery whenever possible.
3. Postpone all delayed breast reconstructions.
 G. Curigliano et al. / The Breast 52 (2020) 8e16 11

Table 2
Prioritization of outpatient visits for patients with breast cancer.

Table 3
Prioritization of surgery in patients with breast cancer.

4. Minimize the use of oncoplastic procedures if they require surgery after 8 weeks allowed.
prolonged hospitalization and/or have a high risk for
complications. 1. Urgent:
5. In case immediate breast reconstruction is considered, recom- a. Patients with significant tumour burden, not responding or
mend simpler (less intensive) procedures with fast recovery progressing under PST.
(microsurgery should not be undertaken e high resources b. Pregnant patients, if surgery upfront was decided by the
needed). multidisciplinary tumour board.
c. Patients with complicated locally advanced tumours not
The following is meant to be a grid of priority in order to otherwise manageable.
minimize the possible detrimental effect of treatment delay in a 2. High Priority
worst-case scenario when the availability of surgical slots is highly a. Patients with early isolated loco-regional recurrence (within
reduced (e.g. 10e20% of the usual activity). We propose to prioritize 48 months from primary treatment).
patients with diagnosed malignancy into 4 categories. 1) Urgent: b. High-risk patients with contraindications to PST, or node
surgery within 2 weeks; 2) High priority: surgery within 4 weeks; positive, or with disease showing biological features of
3) Medium priority: surgery within 8 weeks; 4) Low priority: aggressiveness.
12 G. Curigliano et al. / The Breast 52 (2020) 8e16

3. Intermediate Priority the personnel that is present and the pre-existing treatment
a. Patients treated with PST (ideally at a maximum of 4e6 capacity:
weeks after treatment completion).
b. Pre-menopausal patients with ER þ tumours and without 1. Postpone RT up to 3 months for high-risk and up to 6 months for
indication for preoperative chemotherapy (since neoadjuvant low-risk patients [19].
endocrine therapy is not recommended for these patients
outside of clinical trials). In the past, protocols were based on the common position that
4. Low Priority RT should start as soon as possible following surgery in order to
a. Ductal carcinoma in situ (however, high grade ER negative or increase treatment efficacy. Following population-based data from
very extensive DCIS and/or with palpable lump or extensive a more recent cohort of breast cancer patients, starting RT shortly
microcalcifications might fall into the intermediate priority after surgery does not seem to be associated with a better long-
category based on case by case considerations). term outcome [19].
b. Post-menopausal patients with Luminal A-like cancer. In
these women primary endocrine therapy could be initiated, 2. Moderate hypofractionation should be used for all breast/chest
and surgery could be postponed. wall and nodal RT, e.g. 40Gy in 15 fractions over 3 weeks
[19e21].

The use of moderate hypofractionation is already the standard

1.6. Radiation therapy (Table 4) of care in many countries and in the altered risk-benefit context of a
pandemic should be strongly considered for all patients, including
1.6.1. Early breast cancer (EBC) those after breast reconstruction.
Radiation therapy (RT) for breast cancer is most often delivered
after completion of other treatments, including surgery and 3. Deliver RT in 5 fractions for all patients requiring RT with node
chemotherapy. Conventional treatment duration is between 3 and negative tumours that do not require a boost. Options include
7 weeks. During the COVID-19 pandemic, we need to contribute to 28e30Gy in one weekly fraction over 5 weeks or 26Gy in 5 daily
the statement of the World Health Organization (WHO) “to stop, fractions over 1 week as per the FAST and FAST Forward trials,
contain, control, delay and reduce the impact of this virus at every respectively [22e24].
opportunity”. This translates into minimising exposure and burden
to both patients and healthcare personnel without compromising Five-year local relapse data for FAST Forward will be published
oncological outcome, by minimising the number of hospital visits soon but data on 3-year normal tissue toxicity has already been
and limiting the complexity of RT planning/treatment [18]. A useful demonstrated to be equivalent with 40Gy in 15 fractions.
approach during the pandemic is to give preference, to the least
resource-intensive treatment regimen, provided that there are data 4. Boost RT should be omitted to reduce fractions and/or
supporting the use of this type of regimen. complexity in the vast majority of patients unless those 40 years
The following recommendations can be considered and dis- old and under, or over 40 years with significant risk factors for
cussed with the patients, based on the particular circumstances local relapse [25].
that may be influenced by social restrictions to contain viral spread,
the proportion of the population that is affected, the percentage of

Table 4
Prioritization of radiotherapy in patients with breast cancer.
 G. Curigliano et al. / The Breast 52 (2020) 8e16 13

Boost RT reduces the local recurrence risk without improving paclitaxel when compared to 3-weekly docetaxel. Dose-dense
survival. An example of a significant risk factor is the presence of regimens allow for the shortest duration of treatment.
involved resection margins where further surgery is not possible.  For triple negative EBC, when deciding on the addition of plat-
Any boost should be with a minimum supplementary number of inum to anthracyclines and taxanes, the higher haematological
fractions or given concurrently with the treatment fractions. toxicity and consequent risk of immunosuppression of these
agents must be taken into account during this pandemic, in
5. Accelerated partial breast RT can also be considered for selected particular, considering that the potential additional benefit of
low-risk patients [26e29]. these agents is still controversial.
 For HER2þ EBC, the use of anti-HER2 agents is highly recom-
Accumulating data support the use of partial breast irradiation. mended, as per guidelines, in view of the substantial survival
An accelerated schedule like in the Florence trial, using 30Gy in 5 benefit and the absence of data suggesting any detrimental ef-
fractions over 2 weeks, suits very well. The duration could be fect of their use during this pandemic. In lower risk patients
further reduced by condensing the schedule into a 1-week frac- shortening trastuzumab administration to half year may be
tionation schedule (reducing the total dose) or delivery of intra- considered [32], except for those treated with the APT (weekly
operative electron-based RT that is delivered as a one-step paclitaxel and trastuzumab) regimen. Trastuzumab subcutane-
procedure together with the lumpectomy. ous formulation is preferred and, when resources allow it, home
administration can be used.
6. Omission of RT might be considered in elderly patients at low  For ERþ/HER2 negative EBC, the most difficult decision is
risk of recurrence [30]. related to the use of adjuvant chemotherapy. In cases where the
benefit of this treatment is uncertain, the risk/benefit balance,
The elderly constitutes the population at higher risk to develop during this pandemic, might more often be in favour of not
severe consequences from COVID-19 and at the same time the administering chemotherapy. As for all decision-making process
population of patients who derive the less benefits, in absolute in oncology, the ultimate decision must be taken by the patient,
terms, from postoperative RT. This indication, however, should be after adequate information, since the attitude towards risks and
evaluated in the light of the local situation and reconsidered for the benefits is highly variable according to individuals’ values and
individual patient every 4 weeks. preferences and may be different in the current pandemic sit-
Trials investigating safe omission of RT can be considered if they uation. Genomic tests may be used to help treatment decision-
do not impact on patient visits and resources are available. Centres making in doubtful cases.
may also consider omitting RT for low-risk ductal carcinoma in-situ  Adjuvant endocrine therapy, including the use of ovarian func-
(DCIS) depending on individual risk and benefit. tion suppression in pre-menopausal women, should follow the
usual international guidelines, since no additional risk is fore-
1.7. Advanced breast cancer (ABC) seen from these agents. In selected cases, 3-monthly adminis-
tration of LHRH agonist can be used, provided that confirmation
For ABC, radiation therapy is urgent for the following situations: of ovarian suppression is done; however, in very young women
and/or women taking an aromatase inhibitor, the risk of inad-
1. Treatment of spinal cord compression. equate ovarian suppression with the 3-monthly administration
2. Treatment of brain and leptomeningeal metastases. is higher. In addition, the administration of an LHRH agonist can
3. Palliative treatments (e.g. of bone metastases) not responding to be performed at home, if resources allow it.
pharmaceutical interventions  For adjuvant bisphosphonates, oral formulations can be
preferred during this pandemic. Possible delay of administration
or moving the administration earlier, when resources are still
1.8. Systemic therapy (Table 5) available may also be considered, in particular considering that
the interval of administration of i.v. formulations is every 6
1.8.1. Early breast cancer (EBC) months.
Early breast cancer can be a fatal disease if left untreated -
adequate surgery combined with appropriate perioperative thera-
pies are essential to increase the probability of cure. For this reason, 1.9. Advanced breast cancer (ABC)
treatment of EBC patients should, as much as possible, follow high
quality international clinical guidelines [31]. However, some of the Advanced/metastatic breast cancer is an incurable disease, with
adjuvant systemic therapies have a significant risk of immuno- a median survival of about 3 years, varying according to the breast
suppression that can have detrimental effects during the COVID-19 cancer subtype. In addition, metastatic disease carries in itself some
pandemic. Some measures can be taken to decrease this potential level of immunosuppression. It is therefore essential that all ABC
detrimental effect: patients remain under adequate treatment, according to high
quality international guidelines [33], and close surveillance during
 When utilizing chemotherapy regimens with intermediate/high the COVID-19 pandemic. Notwithstanding these facts, some mea-
risk of immunosuppression, such as anthracyclines, 3-weekly sures may be taken to decrease the risk of complications and allow
docetaxel or 3 weekly platinum, hematopoietic growth factors for adequate treatment of these patients.
can be used to decrease the risk of neutropenia and febrile
neutropenia.  Even under normal (non-pandemic) circumstances, the balance
 Steroids use should be limited to the indispensable, to avoid between quantity and quality of life is crucial in the manage-
increasing the risk of immunosuppression. ment of ABC. This holds equally in the COVID-19 pandemic and
 To decrease the number of visits to the hospital, 2-weekly (dose- more so where treatment options are being cautiously consid-
dense) or 3-weekly regimens should be preferred. However, in ered, underscoring the need for shared decisions with patients.
patients above the age of 65 years, the number of visits should Dose reductions and dose interruptions should be considered,
be balanced with the substantially better tolerability of weekly whenever the side effects are important. In some cases of
14 G. Curigliano et al. / The Breast 52 (2020) 8e16

Table 5
Prioritization of systemic treatment in patients with early and metastatic breast.
 G. Curigliano et al. / The Breast 52 (2020) 8e16 15

prolonged treatments and stable disease, treatment holidays Loneliness is associated with higher risk of mortality in cancer
may be considered but require active and tight surveillance. patients [34,35]. Social distancing is known to have negative health
 For ERþ/HER2 negative ABC, endocrine-based therapy is the consequences and increase risk for premature mortality during
preferred choice for the vast majority of patients and should normal times [36], but it also enhances patients’ feelings of un-
follow the usual international guidelines, including the certainty associated with their prognosis. It is now well docu-
mandatory use of ovarian function suppression in pre- mented that perceived uncertainty increases individual emotional
menopausal women. distress and this in turn has negative effects on clinical outcomes in
 One of the most difficult decisions during the COVID-19 cancer patients [37,38]. Three main aspects explain such uncer-
pandemic relates to the addition of CDK 4/6 inhibitors, in view tainty: patients’ perception of the impact of social isolation and of
of their immunosuppressive effect. These agents are now the healthcare crisis to access the cancer center to continue treat-
considered the standard of care for this subtype of breast cancer ments; the risk of being infected when accessing the cancer center;
but can be used in either 1st or 2nd line. During this pandemic, and the need to change daily habits, especially those recommended
the decision to add a CDK 4/6 inhibitor to endocrine therapy by health professionals as affecting well-being and clinical out-
should take into account the burden of metastatic disease, the comes, such as physical activity. The need to be isolated to contain
pace of disease progression and the possibility of using these the epidemics is a stark contrast to what is normally recommended
agents later in the course of the disease (situation variable in for cancer patients including the importance of outdoor physical
different countries). exercise and of maximizing social supports.
 The addition of an mTOR inhibitor or a Pi3KCA inhibitor to To deal with the increased risk of distress and psychological
endocrine therapy must also take into account their immuno- disorders and the obligation to adhere to social isolation, tele-
suppressive effect and the risk of pneumonitis/interstitial lung medicine has been used also by psychologists and psychiatrists to
disease and other serious side effects, as well as the lack of guarantee psychological individual and group support for patients
survival benefit seen so far from the use of these agents. Deci- while limiting visits to the cancer center. In order to propose the
sion should be made on a case-by-case basis, considering the adequate support to patients, psychological status and associated
burden of metastatic disease, the pace of disease progression, contributing factors should be monitored at different time points of
the possibility of using these agents later in the course of the the care pathway. Hospital Anxiety and Depression Scale (HADS) is
disease, and the availability of other therapeutic options. an easy to use questionnaire and has a good accuracy in assessing
 When utilizing chemotherapy, preference should be given to anxiety and depression in cancer patients [39]. Furthermore, even
oral agents and agents with lower risk of immunosuppression, in presence of low levels of depression and anxiety it will be crucial
such as capecitabine, including for triple negative or HER2þ to identify critical levels of intolerance of uncertainty and feelings
ABC. Vinorelbine can be used in its oral formulation and a dose of loneliness in order to implement interventions to decrease the
reduction can be considered to avoid haematological toxicity. risk of further distress and psychopathological complications.
 In cases where the use of i.v. agents and/or agents with higher
risk of immunosuppression is needed, preference should be Conclusions
given to liposomal formulations of anthracyclines and 3-weekly
regimens of taxanes or platinum compounds. Once again, the In the context of the COVID-19 pandemic, we recommended
number of visits should be balanced with the substantially that routine breast screening be suspended, and that patients with
better tolerability of weekly paclitaxel when compared to 3- early and advanced breast cancer be treated as outpatients as much
weekly docetaxel, in particular for older and/or less fit pa- as possible at the nearest medical center. Exams and appointments
tients. Use of prophylactic hematopoietic growth factors should of patients on follow-up or under adjuvant endocrine therapy
also be considered. should either be postponed or managed through telemedicine.
 For HER2þ ABC, the use of anti-HER2 agents is highly recom- Treatment should follow international guidelines, as much as
mended, as per guidelines, in view of the substantial survival possible, but efforts should be made to minimize the number of
benefit and the absence of data suggesting any detrimental ef- hospital visits. All treatment decisions should be taken in the
fect of their use during this pandemic. context of a multidisciplinary tumour board, which may take place
 The use of bone modulating agents should be discussed on a virtually. All treatment decision-making should balance risk and
case-by-cases basis, depending on the burden of bone disease benefits of treatment in the context of the specific pandemic level,
and the presence/absence of symptoms. In many circumstances, on a case by case discussion, always including patients’ preferences.
it is possible to increase the interval of administration of i.v.
bisphosphonates, limiting the number of visits to the hospital Disclosures of interest statement
while maintaining a good control of bone metastases. Further-
more, the administration of s.c. denosumab can be performed at GC reports grants from Roche, advisory role for Daichii Sankyo,
home, if resources allow it. Astra Zeneca Macrogenics, BMS and Ellipsis, personal fees from
MSD, Astra Zeneca, travel grants from Pfizer, personal fees from
Daichii Sankyo, outside the submitted work;
1.10. Psychological Management of Cancer Patients during the MJC, OG have no financial disclosures.
COVID-19 outbreak PP is a medical advisor for Sordina IORT Technologies spa.
GP reports no conflicts of interest.
The rapid spread of SARS-CoV-2 epidemics and the increased KM reports no conflicts of interest.
risk of clinical severe events in cancer patients occur alongside NH receives funding via a National Breast Cancer Foundation
psychological side effects that worsen patients’ situation. The sig- (NBCF Australia) Breast Cancer Research Leadership Fellowship.
nificant psychological impact on oncological patients is com- OP reports no conflicts of interest.
pounded by multiple factors during the pandemic e knowledge ES reports honoraria: Amgen, AstraZeneca, Clinigen, Egis, Eli
that the individual is at higher risk of serious complication if Lilly, Genomic Health, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz,
infected by Covid-19, loneliness and isolation as a result of social TLC Biopharmaceuticals. Travel support: Amgen, AstraZeneca, Egis,
distancing, and the underlying constant fear of the cancer. Novartis, Pfizer, Roche. Clinical research: Amgen, AstraZeneca,
16 G. Curigliano et al. / The Breast 52 (2020) 8e16

Boehringer, Eli Lilly, Merck, Novartis, Pfizer, Roche, Samsung. of early breast cancer: 10-year follow-up results of two randomised
controlled trials. Lancet Oncol 2013;14(11):1086e94.
FC has consultancy role for Amgen, Astellas/Medivation, Astra-
[21] Whelan TJ, Pignol J-P, Levine MN, et al. Long-term results of hypofractionated
Zeneca, Celgene, Daiichi-Sankyo, Eisai, GE Oncology, Genentech, radiation therapy for breast cancer. N Engl J Med 2010;362(6):513e20.
GlaxoSmithKline, Macrogenics, Medscape, Merck-Sharp, Merus BV, [22] Brunt AM, Haviland J, Sydenham M, et al. FAST phase III RCT of radiotherapy
Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, prIME hypofractionation for treatment of early breast cancer: 10-year results
(CRUKE/04/015). Int J Radiat Oncol Biol Phys 2018;102(5):1603e4.
Oncology, Roche, Sanofi, Samsung Bioepis, Seattle Genetics, Teva. [23] Brunt AM, Wheatley D, Yarnold J, et al. Acute skin toxicity associated with a 1-
week schedule of whole breast radiotherapy compared with a standard 3-
References week regimen delivered in the UK FAST-Forward Trial. Radiother Oncol
2016;120(1):114e8.
[24] Leong N, Truong PT, Tankel K, Kwan W, Weir L, Olivotto IA. Hypofractionated
[1] Livingston E, Bucher K. Coronavirus disease 2019 (COVID-19) in Italy. J Am nodal radiation therapy for breast cancer was not associated with increased
Med Assoc 2020. https://doi.org/10.1001/jama.2020.4344.
patient-reported arm or brachial plexopathy symptoms. Int J Radiat Oncol Biol
[2] Onder G, Rezza G, Brusaferro S. Case-fatality rate and characteristics of pa- Phys 2017;99(5):1166e72.
tients dying in relation to COVID-19 in Italy. J Am Med Assoc 2020. https:// [25] Brunt AM, Haviland J, Sydenham M, et al. OC-0595: FAST-Forward phase 3
doi.org/10.1001/jama.2020.4683. RCT of 1-week hypofractionated breast radiotherapy:3-year normal tissue
[3] Remuzzi A, Remuzzi G. COVID-19 and Italy: what next? Lancet effects. Radiother Oncol 2018;127:S311e2.
2020;395(10231):1225e8. https://doi.org/10.1016/S0140-6736(20)30627-9.
[26] Bartelink H, Maingon P, Poortmans P, et al. Whole-breast irradiation with or
[4] Hollander JE, Carr BG. Virtually perfect? Telemedicine for covid-19. N Engl J without a boost for patients treated with breast-conserving surgery for early
Med 2020. https://doi.org/10.1056/NEJMp2003539.
breast cancer: 20-year follow-up of a randomised phase 3 trial. Lancet Oncol
[5] Ueda M, Martins R, Hendrie P, et al. Managing cancer care during COVID-19 2015;16(1):47e56.
pandemic: agility and collaboration toward a common goal. J Natl Compr [27] Coles CE, Griffin CL, Kirby AM, et al. Partial-breast radiotherapy after breast
Canc Netw 2020;18(4).
conservation surgery for patients with early breast cancer (UK IMPORT LOW
[6] Extance A. Covid-19 and long term conditions: what if you have cancer, dia- trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-
betes, or chronic kidney disease? BMJ 2020;368:m1174.
inferiority trial. Lancet 2017;390(10099):1048e60.
[7] Deming WE. Out of the crisis. 1986. [28] Livi L, Meattini I, Marrazzo L, et al. Accelerated partial breast irradiation using
[8] Liang W, Guan W, Chen R, et al. Cancer patients in SARS-CoV-2 infection: a intensity-modulated radiotherapy versus whole breast irradiation: 5-year
nationwide analysis in China. Lancet Oncol 2020;21(3):335e7. survival analysis of a phase 3 randomised controlled trial. Eur J Canc
[9] NHS. Clinical. Guide for the management of cancer patients during the coro- 2015;51(4):451e63.
navirus pandemic. 2020. https://www.england.nhs.uk/coronavirus/wp-
[29] Veronesi U, Orecchia R, Maisonneuve P, et al. Intraoperative radiotherapy
content/uploads/sites/52/2020/03/Specialty-guide_Cancer-and-coronavirus_ versus external radiotherapy for early breast cancer (ELIOT): a randomised
17-March.pdf. controlled equivalence trial. Lancet Oncol 2013;14(13):1269e77.
[10] Biganzoli L, Cardoso F, Beishon M, et al. The requirements of a specialist breast [30] Kunkler IH, Williams LJ, Jack WJL, Cameron DA, Dixon JM. Breast-conserving
centre. Breast 2020;51:65e84. surgery with or without irradiation in women aged 65 years or older with
[11] ASBrS ACR. ASBrS and ACR joint statement on breast screening exams during
early breast cancer (PRIME II): a randomised controlled trial. Lancet Oncol
the COVID-19 pandemic. 2020. 2015;16(3):266e73.
[12] ASCO. Care of individuals with cancer during COVID-19. 2020. https://www.
[31] Cardoso F, Kyriakides S, Ohno S, et al. Early breast cancer: ESMO Clinical
asco.org/asco-coronavirus-information/care-individuals-cancer-during- Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol
covid-19. 2019;30(10):1674.
[13] ASBrS. Recommendations for prioritization, treatment and triage of breast [32] Earl HM, Hiller L, Vallier A-L, et al. 6 versus 12 months of adjuvant trastu-
cancer patients during the COVID-19 pandemic: executive summary. 2020. zumab for HER2-positive early breast cancer (PERSEPHONE): 4-year disease-
https://www.breastsurgeons.org/docs/news/The_COVID-19_Pandemic_
free survival results of a randomised phase 3 non-inferiority trial. Lancet
Breast_Cancer_Consortium_Recommendations_EXECUTIVE_SUMMARY.pdf? 2019;393(10191):2599e612.
01. [33] Cardoso F, Senkus E, Costa A, et al. 4th ESOeESMO international consensus
[14] ECCO. Statement on COVID-19 from the European cancer organisation’s board guidelines for advanced breast cancer (ABC 4). Ann Oncol 2018;29(8):
of directors. 2020. https://www.ecco-org.eu/Global/News/Latest-News/2020/ 1634e57.
03/NEWS-Statement-on-COVID-19-from-the-European-Cancer-Organisation-
[34] D’Ippolito S, Shams M, Ambrosini E, Calì G, Pastorelli D. R1 - the effect of
Board-of-Directors. loneliness on cancer mortality. Ann Oncol 2017;28:vi82.
[15] ACS. COVID-19. Guidance for triage of non-emergent surgical procedures.
[35] Hill EM, Hamm A. Intolerance of uncertainty, social support, and loneliness in
2020. https://www.facs.org/about-acs/covid-19/information-for-surgeons/ relation to anxiety and depressive symptoms among women diagnosed with
triage. ovarian cancer. Psycho Oncol 2019;28(3):553e60.
[16] ACS. COVID-19. Recommendations for management of elective surgical pro- [36] Holt-Lunstad J, Smith TB, Baker M, Harris T, Stephenson D. Loneliness and
cedures. 2020. https://www.facs.org/about-acs/covid-19/information-for- social isolation as risk factors for mortality: a meta-analytic review. Perspect
surgeons/elective-surgery.
Psychol Sci 2015;10(2):227e37.
[17] ASPS ASPS. Statement on breast reconstruction in the face of COVID-19 [37] Bortolato B, Hyphantis TN, Valpione S, et al. Depression in cancer: the many
pandemic. 2020. https://www.plasticsurgery.org/documents/medical- biobehavioral pathways driving tumor progression. Canc Treat Rev 2017;52:
professionals/COVID19-Breast-Reconstruction-Statement.pdf. 58e70.
[18] Coles CE, Aristei C, Bliss J, et al. International guidelines on radiation therapy [38] Reis JC, Antoni MH, Travado L. Emotional distress, brain functioning, and
for breast cancer during the COVID-19 pandemic. Clin Oncol 2020;32(5):
biobehavioral processes in cancer patients: a neuroimaging review and future
279e81. directions. CNS Spectr 2020;25(1):79e100.
[19] van Maaren MC, Bretveld RW, Jobsen JJ, et al. The influence of timing of ra-
[39] Annunziata MA, Muzzatti B, Bidoli E, et al. Hospital anxiety and depression
diation therapy following breast-conserving surgery on 10-year disease-free Scale (HADS) accuracy in cancer patients. Support Care Canc 2019. https://
survival. Br J Canc 2017;117(2):179e88. doi.org/10.1007/s00520-019-05244-8.
[20] Haviland JS, Owen JR, Dewar JA, et al. The UK Standardisation of Breast
Radiotherapy (START) trials of radiotherapy hypofractionation for treatment