# data[].attributes.body
"Algo (legal/interessante) sobre mim, e que poucas pessoas sabem, é que..."

Eu toco gaita em uma banda de sertanejo universitário

# data[].attributes.body
Chanaya Gutterres

Algo (legal/interessante) sobre mim, é que poucas pessoas sabem, é que ando gosto de andar de patins nas horas livres.

# data[].attributes.body
Eu sou vegetariano e sei bordar pedraria

# data[].attributes.body
eu lutei karatê por anos

# data[].attributes.body
"Algo (legal/interessante) sobre mim, e que poucas pessoas sabem é que..."

Eu faço desenho de anime

# data[].attributes.body
Algo (legal/interessante) sobre mim, que poucas pessoas sabem, é que eu tenho 20 anos de diferença do meu irmão

# data[].attributes.body
Tenho uma irmã gêmea que ta fazendo Medicina também

# data[].attributes.body
Algo (legal/interessante) sobre mim, e que poucas pessoas sabem, é que gosto de desenhar, luto judô desde os 12 e sei tocar piano

# data[].attributes.body
Algo (legal/interessante) sobre mim, e que poucas pessoas sabem, é que gosto muito de ler, principalmente livros de fantasia

# data[].attributes.body
joguei rugby por anos

# data[].attributes.body
Algo legal/interessante sobre mim, e que poucas pessoas sabem, é que eu danço ballet clássico desde os 3 anos de idade.

# data[].attributes.body
Algo (legal/interessante) sobre mim, e que poucas pessoas sabem, é que eu sou filha de um croata.

# data[].attributes.body
sou bastante ligada às artes num geral

# data[].attributes.headline
"Algo (legal/interessante) sobre mim, e que poucas pessoas sabem, é que... amo experimentar coisas novas mas enjoo de tudo muito rápido 

# data[].attributes.subject
"Algo (legal/interessante) sobre mim, e que poucas pessoas sabem, é que... amo experimentar coisas novas mas enjoo de tudo muito rápido 

# data[].attributes.body
Acho legal/interessante sobre mim, e que poucas pessoas sabem, que pratico meditação como forma de me "desligar" da maior parte dos meus problemas pessoais.

# data[].attributes.body
Algo legal/interessante sobre mim, e que poucas pessoas sabem, é que eu faço lives jogando Lol e Valorant (twitch.tv/valentilt_)

# data[].attributes.body
Eu gosto de correr nas horas vagas e também curto jogar futsal

# data[].attributes.body
Algo interessante/legal sobre mim e que poucas pessoas sabem é que eu adoro fazer miçangas e já fiz três tipos de dança

# data[].attributes.body
Eu não desenvolvi os dentes caninos e optei pelo vegetarianismo antes de saber disso KKKKKKK desculpem, foi difícil encontrar algo

# data[].attributes.body
Algo (legal/interessante) sobre mim, que poucas pessoas sabem, é que

# data[].attributes.body
Algo legal sobre mim: faço bolo e pudim

# data[].attributes.body
“Algo (legal/interessante) sobre mim, e que poucas pessoas sabem é que...”
Eu pratico yoga.

# data[].attributes.body
Sou vegetariana e amo desenhar

# data[].attributes.body
adoro tocar violão

# data[].attributes.body
eu cozinho muito bem

# data[].attributes.body
"Algo (legal/interessante) sobre mim, e que poucas pessoas sabem, é que..."
Luxei meu cóccix tentando fazer uma posição de yoga

# data[].attributes.body
algo legal/interessante sobre mim, é que eu curto mtt esporte e jogo (tento) a maioria

# data[].attributes.body
Faço aula de dança desde muito pequena

# data[].attributes.body
Eu sei maquiar e cozinhar muito bem, amo ver series e tenho um doguíneo chamado Sushi! ❤️

# data[].attributes.body
Algo legal sobre mim, e que poucas pessoas sabem, é que eu sou maquiadora profissional

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toco violão e um pouco de piano

# data[].attributes.body
Algo (legal/interessante) sobre mim, e que poucas pessoas sabem, é que eu fiz ginástica olímpica por muitos anos

# data[].attributes.body
algo sobre mim, e que poucas pessoas sabem, é que jogo ff e sou completamente indecisa(libriana)

# data[].attributes.body
Algo legal sobre mim é que toco violão e instrumentos com cordas em geral desde os 5 anos de idade.

# data[].attributes.body
Meus amigos me acham engraçada

# data[].attributes.body
Já quebrei um vaso sanitário "sem querer" numa festa e já lutei kung-fu

# data[].attributes.body
“Algo legal/interessante sobre mim, e que poucas pessoas sabem, é que eu...” sou libriana é muito indecisa por isso não sei o que por aqui kkkkkkkk

# data[].attributes.body
Algo legal sobre mim, e que poucas pessoas sabem, é que toquei violão por muitos anos e gosto de jogar vôlei

# data[].attributes.body
Eu aprendi a velejar em 2016 e em 2018 ganhei uma regata de escoteiros no Paraná. kkkk

# data[].attributes.body
É que sei costurar e trabalhei muitos anos com artesanato em feltro. E amo cachorros 🐕🐕🐕❤️

# data[].attributes.body
Fiz 5 anos de aula de alemão mas hoje em dia sei falar duas frases.  KKKKK

# data[].attributes.body
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n engl j med
nejm.org
1
The
new england journal
o f
medicine
Presentation of Case
Dr. Aditya Bardia:
A 62-year-old woman was evaluated at this hospital after she had
identified a mass in her left breast, confirmed by her physician on physical examina
-
tion, during the pandemic of coronavirus disease 2019 (Covid-19), the disease
caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The patient, who was of Ashkenazi Jewish ancestry, had no known family his
-
tory of breast or ovarian cancer. Medical history included asthma and a fibro
-
adenoma in the left breast, for which she had undergone excisional biopsy 30 years
earlier. Menarche had occurred at 12 years of age and menopause at 54 years of
age; she had not received hormone-replacement therapy.
Physical examination revealed a mass, measuring 3 cm in greatest dimension,
in the left breast. No other masses or axillary lymph nodes were palpable. The
patient underwent imaging studies in accordance with the American College of
Radiology guidelines.
1
Both breasts were imaged, since the patient’s last mammo
-
gram had been obtained 7 years earlier.
Dr. Gary X. Wang:
Mammography revealed an irregular mass with spiculated
margins underlying the skin marker in the left breast, with imaging characteris
-
tics highly suggestive of cancer (Fig.
1A, 1B, and 1C).
2
Subsequent ultrasound
examination revealed a solid, irregular mass in the left breast that measured 3.1 cm
by 1.5 cm by 1.2 cm (Fig.
1D) and normal left axillary lymph nodes. Tissue sampling
with core-needle biopsy under ultrasonographic guidance was performed (Fig.
1E).
Pathological Discussion
Dr. Amy Ly:
Histologic evaluation of the biopsy specimen revealed invasive ductal
carcinoma, grade 2, spanning at least 1.6 cm in greatest dimension. No definitive
lymphovascular invasion or carcinoma in situ was identified (Fig.
2A). Immuno
-
From the Departments of Medicine
(L.M.S., S.J.I., J.A.S., A.B., B.M.), Surgery
(M.C.S.), Radiation Oncology (R.B.J.),
Radiology (G.X.W.), and Pathology (A.L.),
Massachusetts General Hospital, and
the Departments of Medicine (L.M.S.,
S.J.I., J.A.S., A.B., B.M.), Surgery (M.C.S.),
Radiation Oncology (R.B.J.), Radiology
(G.X.W.), and Pathology (A.L.), Harvard
Medical School — both in Boston.
This article was published on July 1, 2020,
at NEJM.org.
DOI: 10.1056/NEJMcpc2002422
Copyright © 2020 Massachusetts Medical Society.
Founded by Richard
C. Cabot
Eric
S. Rosenberg, M.D.,
Editor
Virginia
M. Pierce, M.D., David
M. Dudzinski, M.D., Meridale
V. Baggett, M.D.,
Dennis
C. Sgroi, M.D., Jo‑Anne
O. Shepard, M.D.,
Associate Editors
Kathy
M. Tran, M.D.,
Assistant Editor
Matthew
B. Roberts, M.B., B.S.,
Case Records Editorial Fellow
, Emily
K. McDonald, Tara Corpuz,
Production Editors
Case 22-2020: A 62-Year-Old Woman with Early
Breast Cancer during the Covid-19 Pandemic
Laura
M. Spring, M.D., Michelle
C. Specht, M.D., Rachel
B. Jimenez, M.D.,
Steven
J. Isakoff, M.D., Ph.D., Gary
X. Wang, M.D., Ph.D., Amy Ly, M.D.,
Jennifer
A. Shin, M.D., M.P.H., Aditya Bardia, M.B., B.S., M.P.H.,
and Beverly Moy, M.D., M.P.H.
Case Records
of the
Massachusetts General Hospital
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histochemical staining showed tumor cells that
were strongly and diffusely positive for estrogen
receptor (ER) and progesterone receptor (PR)
(Fig.
2B). Human epidermal growth factor recep
-
tor 2 (HER2) overexpression was equivocal on
immunohistochemical staining. Subsequent flu
-
orescence in situ hybridization for HER2 did not
reveal amplification.
Figure 1.
Imaging Studies of the Breast.
Bilateral mammograms obtained from the craniocaudal and mediolateral oblique views (Panels A and B, respectively)
show a mass in the left breast underlying the skin marker (arrows). At higher magnification (Panel C), the mass ap
‑
pears irregular and spiculated (arrow). An ultrasound image (Panel D) shows a solid, irregular mass, measuring 3.1 cm
by 1.5 cm by 1.2 cm. An image obtained during core
‑
needle biopsy under ultrasonographic guidance (Panel E) shows
the needle positioned within the mass.
A
B
C
D
E
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3
Case Records of the Massachusetts General Hospital
The patient was referred to a breast surgeon
for further evaluation. To carefully consider vari
-
ous therapeutic options, the breast surgeon saw
the patient in a multidisciplinary clinic that in
-
cluded consultants from the radiation oncology
and medical oncology services.
Discussion of Management
Dr. Bardia:
The Covid-19 pandemic poses a major
challenge to the health care system, and several
organizations have released consensus recom
-
mendations for management of breast cancer
during this unprecedented situation.
3-5
Major dif
-
ferences in management before and during the
pandemic are outlined in Table
1, and key prin
-
ciples are reviewed here. First, during this pan
-
demic, although the choice and sequence of
method of treatment may be affected, the overall
goal of management remains cure. Second, the
benefit of treatment needs to be carefully
weighed against the known risks associated with
treatment and against the potential risk of trans
-
mission of SARS-CoV-2 to patients and health
care providers. Third, the treatment regimen may
need to be modified on the basis of the indi
-
vidual clinical and pathological scenario. Finally,
it is important to organize a multidisciplinary
plan of alternative options that can be imple
-
mented in a resource-constrained environment
(Fig.
3).
M a nagemen t of Br e a s t C a ncer
before the Covid-19 Pandemic
Dr. Michelle C. Specht:
The new diagnosis of breast
cancer in this patient gives us an opportunity to
reflect on the ways in which patients were typi
-
cally cared for before the widespread onset of
Covid-19. We can then consider appropriate man
-
agement strategies that can be implemented
during the pandemic.
Upfront Surgical Options
Before the emergence of Covid-19, a patient with
clinical stage T2N0 (according to the tumor–
node–metastasis classification system), hormone
receptor (HR)–positive, HER2-negative breast
cancer, such as this patient, would be a candi
-
date for upfront surgery. Surgical options would
include mastectomy or lumpectomy with radia
-
tion; these approaches are associated with equiv
-
alent disease-free survival.
6
Given the size of this
patient’s breast, the tumor would be resectable;
therefore, most surgeons would recommend
lumpectomy to preserve body image and sexual
sensation.
7,8
Sentinel-node biopsy of the axilla
would be performed at the time of lumpectomy.
The patient would be informed of the risks as
-
sociated with the procedure, including a 17 to
59% risk of reoperation if the surgical margin is
positive, a 3 to 23% risk of lymphedema, and a
less than 10% risk of postoperative infection,
seroma, or hematoma.
9,10
Genetic counseling and
testing would be recommended, because this
patient is of Ashkenazi Jewish ancestry. Although
overall survival among patients who have a
BRCA1
or
BRCA2
mutation is similar after either
breast-conserving therapy or mastectomy, the
risk of a second, contralateral breast cancer after
Figure 2.
Core-Needle Biopsy Specimens of the Breast.
Hematoxylin and eosin staining of a tissue core (Panel A)
shows invasive ductal carcinoma. Immunohistochemi
‑
cal staining (Panel B) shows invasive carcinoma cells
that are strongly and diffusely positive for estrogen
receptor and progesterone receptor.
A
B
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breast-conserving therapy is 26 to 40% at 20
years.
11
Therefore, some women choose bilateral
mastectomy instead of lumpectomy in order to
prevent a second primary cancer.
Options for Systemic Treatment
Dr. Laura M. Spring:
After upfront surgery is per
-
formed, the final pathological interpretation of
the surgical specimen would determine adjuvant
systemic treatment. The mainstay of adjuvant
treatment for an HR-positive, HER2-negative
tumor is endocrine therapy, and some patients
also receive chemotherapy. Because this patient
is postmenopausal, daily treatment with an aro
-
matase inhibitor for 5 to 10 years
12,13
or upfront
treatment with tamoxifen, followed by an aro
-
matase inhibitor, would be the most likely treat
-
ment choice.
14
Standard clinicopathological features are used
to determine whether a patient with HR-positive,
HER2-negative breast cancer should receive adju
-
vant chemotherapy before endocrine therapy to
further reduce the risk of recurrence. Additional
genomic tests such as an RNA-based risk-score
assay can be performed to estimate both the risk
of recurrence and the potential for risk reduction
with chemotherapy.
12,15-18
For example, the 21-gene
recurrence-score assay Oncotype DX (Genomic
Health) is a gene-expression assay that evaluates
16 cancer-related genes involved in tumor-cell
proliferation and hormonal response, along with
5 reference genes; scores range from 0 to 100.
15
A high recurrence score (defined as either ≥31 or
≥26, depending on the specific trial) is associ
-
ated with a greater risk of distant recurrence and
is predictive of chemotherapy benefit, whereas a
low score (<11) indicates a low risk of recurrence
and limited benefit with chemotherapy.
15
Chemo
-
therapy can also be safely omitted in patients
who have an intermediate score (11 to 25), on
the basis of the Trial Assigning Individualized
Options for Treatment (TAILORx) study, which
showed that efficacy outcomes associated with
adjuvant endocrine therapy and with chemothera
-
Table 1.
General Management of Select Early Breast Cancer Scenarios before and during the Covid-19 Pandemic.*
Clinical Scenario
Typical Management, before Covid-19 Pandemic
Modified Management, during Covid-19 Pandemic†
Newly diagnosed post
‑
menopausal early HR
‑
positive, HER2
‑
negative
breast cancer
Stage I–II: Upfront surgery, followed by adjuvant en
‑
docrine therapy (with or without adjuvant chemo
‑
therapy, radiation therapy, or both).
Stage III: Neoadjuvant therapy, followed by surgery,
radiation therapy, and adjuvant therapy.
Stage I–II: Neoadjuvant therapy (endocrine therapy
preferred), followed by surgery (with or without ad
‑
juvant chemotherapy, radiation therapy, or both).
Stage III: Neoadjuvant therapy (endocrine therapy pre
‑
ferred), followed by surgery and radiation therapy
(with or without adjuvant chemotherapy).
Newly diagnosed pre
‑
menopausal early HR
‑
positive, HER2
‑
negative
breast cancer
Stage I–II: Upfront surgery, followed by adjuvant en
‑
docrine therapy (with or without adjuvant chemo
‑
therapy, radiation therapy, or both).
Stage III: Neoadjuvant chemotherapy, followed by
surgery, radiation therapy, and adjuvant endocrine
therapy with ovarian suppression.
Stage I: Neoadjuvant therapy (endocrine therapy pre
‑
ferred), followed by surgery (with or without adju
‑
vant chemotherapy, radiation therapy, or both).
Stage II–III: Neoadjuvant therapy (endocrine therapy
preferred), followed by surgery, adjuvant chemo
‑
therapy, and radiation therapy.
Newly diagnosed localized
HER2
‑
amplified breast
cancer
Stage I: Upfront surgery, followed by adjuvant HER2
‑
targeted therapy (with or without radiation therapy).
Stage II–III: Neoadjuvant HER2
‑
targeted therapy,
followed by surgery and adjuvant HER2
‑
targeted
therapy (with or without radiation therapy).
Stage I: Modified neoadjuvant HER2
‑
targeted therapy,
followed by surgery and adjuvant HER2
‑
targeted
therapy (with or without radiation therapy).
Stage II–III: Neoadjuvant HER2
‑
targeted therapy,
followed by surgery and adjuvant HER2
‑
targeted
therapy (with or without radiation therapy).
Newly diagnosed localized
triple
‑
negative breast
cancer
Stage I: Upfront surgery, followed by adjuvant chemo
‑
therapy (with or without radiation therapy).
Stage II–III: Neoadjuvant chemotherapy, followed by
surgery (with or without radiation therapy).
Stage I: Neoadjuvant chemotherapy, followed by sur
‑
gery (with or without radiation therapy).
Stage II–III: Neoadjuvant chemotherapy, followed by
surgery (with or without radiation therapy).
*
Of note, these are broad treatment principles, and there could be exceptions. Ultimately, management of breast cancer needs to
be individual
‑
ized. HER2 denotes human epidermal growth factor receptor 2, and HR hormone receptor.
†
If chemotherapy is deemed absolutely necessary during the Covid
‑
19 pandemic, it is important to consider alterations to chemotherapy regi
‑
mens, including minimizing glucocorticoid use, to decrease the extent of myelosuppression. Once
‑
weekly paclitaxel could be substituted for
paclitaxel given every 2 weeks, with the trade
‑
off of the need for a greater number of visits. Alternatively, docetaxel given every 3 weeks can
be used, with growth factor support. For HER2
‑
positive tumors with homogeneous HER2 expression, trastuzumab emtansine (with or with
‑
out pertuzumab) could be considered instead of chemotherapy, particularly for smaller tumors. For stage I triple
‑
negative breast cancer,
docetaxel plus cyclophosphamide may be considered, although for patients for whom chemotherapy is not otherwise recommended, su
r
‑
gery should remain a high priority.
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Case Records of the Massachusetts General Hospital
py plus endocrine therapy were similar, although
a subgroup analysis suggested some benefit with
the addition of chemotherapy among women
who were 50 years of age or younger and had
lower recurrence scores.
19
If we assume that this patient’s pathological
results are consistent with the clinical stage
T2N0, grade 2 tumor, performing a genomic as
-
say is recommended, given that she has certain
features that support the use of chemotherapy
(e.g., large tumor size) and other features that
do not support the use of chemotherapy (e.g.,
strongly HR-positive tumor). If her recurrence
score indicates a chemotherapy benefit, a regi
-
men such as docetaxel and cyclophosphamide
would be a reasonable choice.
20,21
Options for Radiation Therapy
Dr. Rachel B. Jimenez:
Before the Covid-19 pandemic,
radiation therapy would typically be considered
after lumpectomy to reduce the risk of a recur
-
rence in the same breast and to increase sur
-
vival.
22
Treatment with radiation usually begins
4 to 8 weeks after surgery unless chemotherapy
Figure 3.
Multidisciplinary Approach for Management of Early Breast Cancer during the Covid-19 Pandemic.
Ideally, the multidisciplinary team would include a surgical oncologist, a radiation oncologist, a medical oncologist,
a genetics expert (if needed), a social worker (if needed), and a person with expertise in symptom management,
palliative medicine, or both (if needed). If a patient does not undergo upfront surgery, the chemotherapy regimen
that would have been selected for adjuvant therapy can be administered as neoadjuvant therapy to allow for de
‑
ferred surgery.
Multidisciplinary team discussion
Diagnosis of early breast cancer
Ideal candidate for neoadjuvant therapy
Proceed with neoadjuvant therapy
Ideal candidate for upfront surgery
Upfront surgery feasible
Proceed with surgery
Determine whether candidate
for adjuvant therapy
Yes
Initiate additional therapy
on basis of baseline risk and
surgical pathological results
No
Designate surgery
as high priority
No
No
Yes
Yes
Complete neoadjuvant
therapy
Monitor patient closely
Concern for disease
progression (at any time)
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is given, in which case radiation therapy starts
once chemotherapy is complete, since delaying
chemotherapy may reduce its effectiveness.
23
In
the United States, radiation treatment has histori
-
cally been administered daily to the entire breast
over the course of approximately 4.5 to 5 weeks,
often followed by a 1-to-1.5-week radiation
“boost” focused on the area within a few centi
-
meters of the lumpectomy cavity. However, ran
-
domized trials have shown that the efficacy and
safety of “hypofractionated” regimens lasting 3 to
4 weeks are similar to those of “conventional”
fractionation, and therefore, such regimens are
preferred over conventional fractionation for most
patients.
24
Accelerated partial breast irradiation,
which is used to treat only the area immediately
around the lumpectomy cavity over the course of
1 to 2 weeks, is an option for select patients.
25-27
M a nagemen t of Br e a s t C a ncer
during the Covid-19 Pandemic
Dr. Specht:
On March 15, 2020, the Massachusetts
Department of Public Health issued an order to
suspend nonessential elective invasive procedures
to protect patients and health care workers and to
conserve hospital resources during the Covid-19
pandemic. With this mandate, the multidisci
-
plinary treatment of this patient with newly diag
-
nosed breast cancer changed. The risks associated
with surgery during the pandemic — including
patient and staff exposure to SARS-CoV-2 and
the need for personal protective equipment, ven
-
tilators, and medical staff who could otherwise
be deployed to care for patients with Covid-19
— were weighed against the risk of tumor pro
-
gression while the patient was receiving sys
-
temic therapy. Alternative therapeutic options
were discussed in the multidisciplinary clinic.
Approaches to Radiation Therapy
Dr. Jimenez:
During the Covid-19 pandemic, a few
treatment options can be considered regarding
the administration of radiation therapy after sur
-
gery. First, the initiation of radiation therapy
after breast-conserving surgery can be delayed
in order to limit a patient’s exposure to health care
facilities. Several retrospective studies showed
that, among patients who were not receiving
chemotherapy, the efficacy of radiation therapy
was not affected by delaying the start of radia
-
tion up to 20 weeks after breast-conserving
surgery.
28-30
Second, radiation therapy courses
can be shortened with the use of hypofraction
-
ated regimens or accelerated partial-breast irra
-
diation for certain patients and by omitting a
boost in some patients.
24,27,31
Administering the
radiation boost simultaneously with the delivery
of whole-breast radiation can also shorten the
duration of radiation therapy, although results of
randomized trials comparing such an approach
with sequential boosts are not yet available.
32
So-
called “ultrahypofractionated” regimens, in which
the entire breast is treated once weekly for 5 weeks
or daily over the course of 5 consecutive days,
have shown acceptable short-term tumor control
and rates of toxic effects, although the long-
term efficacy and safety of these regimens are
incompletely established; therefore, such a reg
-
imen should be used selectively, even during
the Covid-19 pandemic.
33-36
Options for Neoadjuvant Endocrine Therapy
in Lieu of Surgery
Dr. Spring:
In lieu of upfront surgery, an alterna
-
tive treatment option for this patient would be
preoperative (neoadjuvant) therapy.
12,37
Neoadju
-
vant endocrine therapy has been shown to im
-
prove surgical outcomes by increasing rates of
eligibility to undergo breast-conserving therapy
and by increasing response rates.
38-40
Such ther
-
apy would be an option for this patient even in
the pre–Covid-19 era, although it is vastly under
-
used in the United States.
41
It is well established that aromatase inhibi
-
tors are more effective than tamoxifen when used
as neoadjuvant therapy in postmenopausal wom
-
en.
40,42-46
Initiation of treatment with an aroma
-
tase inhibitor before lumpectomy could lead to a
partial or complete response, thereby increasing
the likelihood of negative surgical margins and
an improved cosmetic outcome. In one study,
69.8% of the patients had a partial or complete
response after receiving an aromatase inhibitor
for 3 months.
47
The risk of disease progression
while a patient is receiving neoadjuvant endo
-
crine therapy is low. Furthermore, during the
period when neoadjuvant therapy is adminis
-
tered, results from genetic testing would typi
-
cally become available, allowing the patient to
make a more informed surgical decision regard
-
ing breast-conserving therapy or mastectomy.
This approach also allows identification of
endocrine-sensitive disease, thereby enabling
some patients to avoid chemotherapy.
37,48
A small
number of randomized clinical trials have shown
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that the response rates and rates of breast-con
-
serving therapy associated with neoadjuvant en
-
docrine therapy are similar to those associated
with neoadjuvant chemotherapy in the appropri
-
ate patient population, while neoadjuvant endo
-
crine therapy confers fewer adverse effects.
38,39,49
The duration of neoadjuvant endocrine therapy is
typically 3 to 6 months, although treatment can
be extended if the tumor continues to respond;
response rates are generally higher when the
duration of treatment is longer.
50
One potential concern associated with neo
-
adjuvant endocrine therapy is the risk of disease
progression. Therefore, timely follow-up exami
-
nation and imaging, if indicated, are important
to monitor for progression. Furthermore, it is
reasonable to perform a genomic analysis of the
diagnostic core-needle biopsy specimen to as
-
sess whether neoadjuvant chemotherapy should
be considered instead of neoadjuvant endocrine
therapy when the decision is not clear. Although
the validation of genomic assays has occurred
mostly for adjuvant treatment, emerging clinical
response data from studies evaluating the use of
neoadjuvant therapy have become available. In
the TransNEOS study, among patients who re
-
ceived neoadjuvant letrozole, the incidence of
disease progression was low if the score on the
21-gene recurrence-score assay was below 31
(<1% among patients with a score of <18 and 4%
among those with a score of 18 to 30); in con
-
trast, the incidence of progression was consider
-
ably higher among patients with a score of 31 or
higher (17%).
51
If this patient’s recurrence score
is found to be 31 or higher, a multidisciplinary
discussion and consideration of resources would
be needed to determine whether the patient
should proceed to surgery or begin neoadjuvant
chemotherapy.
The clinical scenario is more complicated
among premenopausal women, given the paucity
of data with neoadjuvant endocrine therapy; most
phase 3 randomized trials evaluating this treat
-
ment have focused on postmenopausal women.
Although the randomized phase 2 GEICAM/
2006-03 study showed a significant benefit of
neoadjuvant chemotherapy over neoadjuvant en
-
docrine therapy among premenopausal women,
with higher response rates seen among those who
had a high Ki-67 proliferation index (a marker of
cellular proliferation), the use of neoadjuvant
endocrine therapy remains a valid approach in
the appropriate clinical situation.
12,37,38
With re
-
gard to choice of endocrine therapy, the STAGE
study showed that neoadjuvant treatment with
an aromatase inhibitor plus a luteinizing hor
-
mone–releasing hormone (LHRH) agonist result
-
ed in significantly greater response rates than
an LHRH agonist plus tamoxifen.
45
However, the
length of time it takes the combination of an
aromatase inhibitor and an LHRH agonist to
suppress estrogen — with maximal suppression
typically achieved by week 4 — is a potential
concern.
45
During the Covid-19 pandemic, the ad
-
ministration of an LHRH agonist every 3 months
is preferred over a monthly dose to minimize
clinic visits. As noted previously, performing a
genomic analysis of the core-needle biopsy spec
-
imen is a reasonable approach to determine
whether chemotherapy would be appropriate. Al
-
though the threshold for recommending chemo
-
therapy is lower for women 50 years or age or
younger, on the basis of the results of the TAILORx
study,
19
it is important to balance the potential
benefit of chemotherapy with the risk of immu
-
nosuppression during the Covid-19 pandemic;
moreover, the potential role of suppression of
ovarian function in lieu of chemotherapy among
patients who have a lower clinical risk should
also be carefully considered.
52
With regard to
this patient, the core-needle biopsy specimen
was sent for genomic analysis, which revealed
an intermediate recurrence score of 24 on the
21-gene assay.
A lter nati v e Scena r ios dur ing
the Covid-19 Pandemic
Dr. Beverly Moy:
Although this patient has clinical
stage T2N0, HR-positive, HER2-negative breast
cancer, we also want to consider appropriate
treatment strategies for women who present
with other subtypes of breast cancer during the
pandemic.
Patients with HER2-Amplified Breast Cancer
A widely accepted evidence-based treatment ap
-
proach used in patients with early HER2-positive
breast cancer is surgery, followed by adjuvant
therapy, for patients with clinical stage T1N0
disease and neoadjuvant systemic therapy, fol
-
lowed by surgery, for patients with clinical stage
T2–4N0 or node-positive disease.
53,54
On the basis
of this approach, the preferred initial treatment
for a patient with clinical stage T2N0 HER2-
positive breast cancer — even in the absence of
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8
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The
new england journal
o f
medicine
the Covid-19 pandemic — would be neoadjuvant
therapy. This approach is based in part on the
KATHERINE trial, which showed improved out
-
comes with the use of adjuvant trastuzumab
emtansine (T-DM1) among women with early
HER2-positive breast cancer who had had resid
-
ual invasive disease after receiving multiagent,
HER2-targeted neoadjuvant therapy.
54
However,
the Covid-19 pandemic has led oncologists to
more carefully weigh the risks and the benefits
of standard neoadjuvant HER2-targeted regimens.
Commonly used regimens that have been
evaluated extensively in clinical trials include
doxorubicin and cyclophosphamide, followed by
paclitaxel, trastuzumab, and pertuzumab, as well
as combination therapy with docetaxel, carbo
-
platin, trastuzumab, and pertuzumab.
55,56
Although
these evidence-based regimens are extremely
efficacious, they are also associated with a high
degree of immunosuppression, and their use
could lead to further consequences if a patient be
-
comes infected with SARS-CoV-2. The KRISTINE
trial evaluated the effects of replacing standard
neoadjuvant HER2-targeted regimens with a less
immunosuppressive regimen, T-DM1 plus per
tuz
u
-
mab.
57
In that trial, despite being associated
with fewer toxic effects, neoadjuvant treatment
with T-DM1 plus pertuzumab led to a lower
pathological complete response rate than combi
-
nation therapy with docetaxel, carboplatin,
trastuzumab, and pertuzumab (44.4% vs. 55.7%),
possibly because a strictly HER2-targeted ther
-
apy approach may be less active among patients
whose cancer has heterogeneous HER2 expres
-
sion. Another alternative neoadjuvant regimen is
paclitaxel administered with trastuzumab and
pertuzumab, which will be more carefully studied
in the upcoming COMPASS trial (ClinicalTrials.gov
number, NCT04266249). The downside of treat
-
ment with paclitaxel, trastuzumab, and pertuzu
-
mab is that the weekly dose of paclitaxel re
-
quires frequent trips to a clinic. Adjustment of
the chemotherapy regimen, whereby paclitaxel or
docetaxel could be administered every 3 weeks,
could be performed, but the use of granulocyte
colony-stimulating factors to reduce immuno
-
suppression during the pandemic should be
considered.
If a patient has a small clinical stage T1N0
HER2-positive tumor, the surgical restrictions
resulting from the Covid-19 pandemic could
prevent a standard upfront surgical approach.
Therefore, neoadjuvant systemic therapy is need
-
ed, but there is no clear standard regimen. In the
absence of clear pathological confirmation of
lymph-node status, it may not be advisable to
eliminate the use of pertuzumab, since it is as
-
sociated with modest benefit regarding disease-
free survival in early HER2-positive breast cancer.
58
Therefore, reasonable neoadjuvant regimens in
this context include paclitaxel, trastuzumab, and
pertuzumab or T-DM1 plus pertuzumab.
Patients with Triple-Negative Breast Cancer
Dr. Steven J. Isakoff:
Chemotherapy remains the
cornerstone of systemic treatment for early ER-
negative, PR-negative, HER2-negative (triple-neg
-
ative) breast cancer. For this patient with clinical
stage T2N0 cancer, the standard approach for
triple-negative breast cancer before the Covid-19
pandemic would have involved neoadjuvant che
-
motherapy with deferred surgery, and this remains
the preferred approach during the pandemic. In
addition to facilitating successful surgical resec
-
tion, the neoadjuvant approach allows for the
response to neoadjuvant therapy to inform adju
-
vant therapy decisions; in the Capecitabine for Re
-
sidual Cancer as Adjuvant Therapy (CREATE-X)
trial, treatment with adjuvant capecitabine showed
a survival benefit among patients with HER2-
negative breast cancer who had had residual
disease after receiving anthracycline-based neo
-
adjuvant therapy.
59
The neoadjuvant regimens
used for triple-negative breast cancer tumors
that are larger than 2 cm in diameter or that are
node-positive typically include an anthracycline
and taxane.
12
The addition of neoadjuvant carbo
-
platin remains controversial; although patho
-
logical complete response rates are higher with
the addition of carboplatin,
60,61
the effect on long-
term outcomes remains uncertain, and, espe
-
cially during the Covid-19 pandemic, the added
risks of hematologic toxic effects and immuno
-
suppression must be carefully considered.
Among patients with triple-negative breast
cancer tumors that measure 2 cm or less in di
-
ameter and are node-negative, administration of
adjuvant chemotherapy is standard practice for
patients with tumors larger than 1 cm in diam
-
eter (T1c) and is often considered for patients
with tumors larger than 0.5 cm in diameter
(T1b).
12
However, if access to surgery is limited
because of the Covid-19 pandemic, the chemo
-
therapy regimen that would have been selected
for adjuvant therapy can be administered as neo
-
adjuvant therapy to allow for deferred surgery.
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n engl j med
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9
Case Records of the Massachusetts General Hospital
For example, docetaxel and cyclophosphamide, a
regimen commonly used for adjuvant therapy,
21
may be administered as neoadjuvant therapy.
62
Surgery should remain a high priority for pa
-
tients whose triple-negative breast cancer tumors
are small and for whom chemotherapy is not
otherwise recommended
3
; alternative systemic
approaches are not suitable for smaller tumors,
and the biologic characteristics of triple-negative
breast cancer arouse concern that a sustained
delay in surgery could result in tumor growth
and upstaging, which in turn may increase the
risk of recurrence.
Patients Who Have Completed Neoadjuvant
Therapy and Need Surgery
Dr. Isakoff:
Patients completing neoadjuvant che
-
motherapy regimens during the Covid-19 pan
-
demic who are unable to proceed to surgery
because of limitations in hospital resources re
-
quire special attention to ensure that long-term
outcomes are not compromised. As a general
principle, surgery for patients who have progres
-
sion of disease during neoadjuvant therapy or
who have no alternative systemic therapy options
is given high priority.
3
Patients with HR-positive
breast cancer who are receiving neoadjuvant en
-
docrine therapy without clinical progression may
safely continue endocrine therapy for 6 months
or more, with the timing of surgery depending
largely on factors relating to hospital resources.
For patients with HER2-positive disease, several
options are available, depending on the response
to neoadjuvant therapy. For patients who have a
clinical complete response or a substantial par
-
tial response, continuation of trastuzumab and
pertuzumab as maintenance treatment may be
reasonable. In addition, taxane-based HER2-
targeted therapy may be safely continued if not
limited by the development of adverse effects.
63
For patients with HER2-positive disease who
have minimal clinical response or no response,
surgery is preferred, but such patients may tran
-
sition to neoadjuvant treatment with T-DM1 un
-
til surgery is feasible, with plans to continue
adjuvant therapy.
54
It is recommended that sur
-
gery for patients who have triple-negative breast
cancer and are completing neoadjuvant therapy
be given high priority.
3
If surgery is not feasible
within a reasonable time frame after completion
of a standard regimen of neoadjuvant therapy,
patients may receive additional cycles of non
-
anthracycline chemotherapy, such as weekly pa
-
clitaxel, capecitabine, or other agents, to provide
a bridge to surgery; however, surgery should be
completed as soon as feasible.
Communic ation w i th Patien t s
during the Covid-19 Pandemic
Dr. Jennifer A. Shin:
During the Covid-19 pandemic,
providers are faced with the challenge of com
-
municating with patients about their cancer di
-
agnosis and treatment plan, while also address
-
ing concerns about Covid-19 and how it might
affect cancer care. An additional challenge is
that these conversations may be occurring virtu
-
ally, rather than in person. Patients may express
feeling overwhelmed by a breast cancer diagno
-
sis and the associated therapies. In the Covid-19
era, patients may have additional anxiety and
fear about coming to the hospital or about the
possibility that administration of cancer thera
-
pies may increase their risk of Covid-19 and
death.
64,65
Patients may also be concerned about
a treatment plan that deviates from routine stan
-
dard of care and whether this alternative ap
-
proach could affect their clinical outcome.
Communication is at the core of the medical
profession, and effective and empathic commu
-
nication can have a positive effect on a patient’s
quality of life, satisfaction with care, and medi
-
cal outcomes.
66-68
During a clinical visit, identi
-
fying and addressing concerns and emotions are
a key first step before proceeding to the other
parts of the visit.
68,69
It is difficult for a patient
to absorb medical information if the provider
does not acknowledge any worry, anxiety, and
distress about the diagnosis and the pandemic.
At the start of the visit, checking in with the
patient is important. This patient may express
worry about the delay in her breast surgery and
may ask whether this might affect her cancer
outcome.
Follow-up
Dr. Bardia:
After discussing the care of this pa
-
tient during a virtual multidisciplinary tumor
board conference, we determined that upfront
surgery was not an option because of Covid-19
restrictions; consequently, neoadjuvant endocrine
therapy with an aromatase inhibitor was initi
-
ated. The patient is currently doing well and has
a 2-month follow-up visit scheduled with the
multidisciplinary team.
The New England Journal of Medicine
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10
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The
new england journal
o f
medicine
Final Diagnosis
Invasive ductal carcinoma of the left breast,
clinical prognostic stage IB (T2N0), estrogen
receptor–positive, progesterone receptor–positive,
human epidermal growth factor receptor 2–nega
-
tive, grade 2, with an intermediate recurrence
score on the 21-gene assay.
Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.
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