Thursday 6 July 2023
Thursday 30 March 2023
Breast Surgery Bulletin - April 2023
by K. Bokkers,
E.M.A. Bleiker, M.E. Velthuizen, R. Koelemij, J.P.J. Burgmans, J.H.
Klinkenbijl, A.P. Schouten van der Velden, N. Vermulst, B.F. Huizinga, A.J.
Witkamp, T. Frakking, R.M. Brohet, C.M. Aalfs, W. Koole, E.J.P. Schoenmaeckers,
M.G.E.M. Ausems
The Breast: Published: March 29, 2023
Background
Pre-test genetic
counseling of patients with breast cancer is increasingly being offered by
non-genetic healthcare professionals. We aimed to evaluate the experiences of
patients with breast cancer receiving pre-test genetic counseling from a
non-genetic healthcare professional (i.e., surgeon or nurse).
Methods
Patients who were
diagnosed with breast cancer and received pre-test counseling from their
surgeon or nurse (mainstream group), and patients who received pre-test
counseling from a clinical geneticist (usual care group) were invited to
participate in our multicenter study. Between September 2019 and December 2021,
patients received a questionnaire after pre-test counseling (T0) and four weeks
after receiving their test results (T1) to evaluate psychosocial outcomes,
knowledge, discussed topics and satisfaction.
Results
We included 191
patients in our mainstream and 183 patients in our usual care group and
received, respectively 159 and 145 follow-up questionnaires. Levels of distress
and decisional regret were comparable in both groups. Decisional conflict was
higher in our mainstream group (p = 0.01), but only 7% had clinically relevant
decisional conflict (vs 2% in usual care group). The possible implications of a
genetic test on (secondary) breast or ovarian cancer risks were less frequently
discussed in our mainstream group (p = 0.03 and p = 0.000, respectively). In
both groups knowledge about genetics was comparable, satisfaction was high and
the majority of patients in both groups preferred to give both verbal and
written consent for genetic testing.
Conclusion
Mainstreamed
genetic care provides sufficient information for the majority of breast cancer
patients to decide about genetic testing with minimal distress.
Optimising post-operative radiation therapy after oncoplastic
and reconstructive procedures
by Trine Tramm,
Orit Kaidar-Person
The Breast: Published: March 28, 2023
Abstract
Surgical techniques for breast cancer have been refined over
the past decades to deliver an aesthetic outcome as close as possible to the
contralateral intact breast. Current surgery further allows excellent aesthetic
outcome even in case of mastectomy, by performing skin sparing or nipple
sparing mastectomy in combination with reconstruction. In this review we
discuss how to optimise post-operative radiation therapy after oncoplastic and
breast reconstructive procedures, including dose, fractionation, volumes,
surgical margins, and boost application.
Highlights
• New surgical procedures for breast cancer poses new
challenges for the radiation oncologists.
• Oncoplastic breast surgery may question the ability to
apply or the need for a tumour bed boost.
• Skin sparing/nipple sparing mastectomies should be planned
to assure clear superficial margins.
• Radiation therapy indications, target volumes, dose and
fractionation should be adapted per case to provide maximal clinical benefit
and reduce toxicity.
• Multidisciplinary teamwork is needed from the time of
diagnosis to plan the most appropriate locoregional therapy.
Tissue- and liquid biopsy-based biomarkers for immunotherapy in
breast cancer
by Luca Licata,
Marco Mariani, Federico Rossari, Giulia Viale, Giulia Notini, Matteo Maria
Naldini, Carlo Bosi, Marta Piras, Matteo Dugo, Giampaolo Bianchini
The Breast: Published: March 27, 2023
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionized
cancer therapy and now represent the mainstay of treatment for many tumor
types, including triple-negative breast cancer and two agnostic registrations.
However, despite impressive durable responses suggestive of an even curative
potential in some cases, most patients receiving ICIs do not derive a
substantial benefit, highlighting the need for more precise patient selection
and stratification. The identification of predictive biomarkers of response to
ICIs may play a pivotal role in optimizing the therapeutic use of such
compounds. In this Review, we describe the current landscape of tissue and
blood biomarkers that could serve as predictive factors for ICI treatment in
breast cancer.
The integration of these biomarkers in a “holistic”
perspective aimed at developing comprehensive panels of multiple predictive
factors will be a major step forward towards precision immune-oncology.
by Damiano Gentile,
Andrea Sagona, Camilla De Carlo, Bethania Fernandes, Erika Barbieri, Simone Di
Maria Grimaldi, Flavia Jacobs, Giulia Vatteroni, Lorenzo Scardina, Ersilia
Biondi, Valeriano Vinci, Rubina Manuela Trimboli, Daniela Bernardi, Corrado
Tinterri
The Breast: Published: March 27, 2023
Introduction
Residual tumor cellularity
(RTC) and pathologic complete response (pCR) after neo-adjuvant chemotherapy
(NAC) are prognostic factors associated with improved outcomes in breast cancer
(BC). However, the majority of patients achieve partial pathologic response
(pPR) and no clear correlation between RTC patterns and outcomes was described.
Our aims were to define predictive factors for pCR and compare different
outcomes of patients with pCR or pPR and with different RTC patterns.
Materials and
methods
Baseline and
post-NAC demographics, clinicopathological characteristics, post-operative
data, survival and recurrence status were recorded from our institutional
database. A multivariable analysis was performed using a logistic regression
model to identify independent predictors of pCR. Disease-free survival (DFS),
distant disease-free survival (DDFS), and overall survival (OS) analyses were
performed using the Kaplan-Meier method.
Results
Overall, of the 495
patients analyzed, 148 (29.9%) achieved pCR, 347 (70.1%) had pPR, and the
median RTC was 40%. Multivariable analysis identified 3 independent factors
predictive of pCR: tumor stage before NAC (cT1-2 84.5% versus cT3-4
15.5%), BC sub-type (HER2-positive 54.7% versus triple-negative
29.8% versus luminal-like 15.5%), and vascular invasion (absence
98.0% versus presence 2.0%). We found statistically significant
longer DFS, DDFS, and OS in patients with pCR and with RTC <40%; no
difference was observed in terms of OS between RTC <40% and RTC ≥40% groups.
Conclusions
Tumor stage before
NAC, BC sub-type, and vascular invasion are significant and independent factors
associated with pCR. Patients with pCR and with RTC <40% have longer DFS,
DDFS, and OS compared with patients with pPR.
by Hope S. Rugo,
Xianchen Liu, Benjamin Li, Lynn McRoy, Rachel M. Layman, Adam Brufsky
The Breast: Published: March 27, 2023
Background
Palbociclib, the
first available cyclin-dependent kinase 4/6 inhibitor, plus endocrine therapy
is approved for hormone receptor-positive/human epidermal growth factor
receptor 2-negative (HR+/HER2-) metastatic breast cancer (MBC). This study
compared real-world effectiveness of palbociclib plus letrozole versus
letrozole in older patients with MBC in US clinical practice.
Methods
This retrospective
analysis included patients from the Flatiron Health longitudinal database.
Overall, 796 women with HR+/HER2- MBC aged ≥65 years starting palbociclib plus
letrozole or letrozole as first-line therapy between February 2015 and
September 2018 were included. Patients were evaluated from treatment start
until December 2018, death, or last visit, whichever came first. Real-world
progression-free survival (rwPFS), overall survival (OS), and real-world best
tumor responses (rwBTR) were endpoints. Stabilized inverse probability
treatment weighting (sIPTW) balanced patient characteristics.
Results
After sIPTW, 450
patients treated with palbociclib plus letrozole and 335 treated with letrozole
were included; median age was 74.0 years. Median rwPFS was 22.2 (95% CI,
20.0–30.4) months for palbociclib plus letrozole versus 15.8 (12.9–18.9) months
for letrozole (hazard ratio, 0.59 [0.47–0.74]; P < 0.001). Median OS
was not reached for palbociclib plus letrozole versus 43.4 months (30.0-not
estimable) with letrozole (hazard ratio, 0.55 [0.42–0.72]; P < 0.001).
No interactions between age groups (65–74 and ≥ 75 years) and treatment groups
were observed for rwPFS or OS. Rate of rwBTR was significantly higher for
palbociclib plus letrozole (52.4%) versus letrozole (22.1%; odds ratio, 2.0
[1.4–2.7]; P < 0.001).
Conclusion
This analysis
demonstrates the effectiveness of palbociclib combination therapy as
standard-of-care for older patients with HR+/HER2- MBC in the first-line
setting.
Future potential targets of antibody-drug conjugates in breast
cancer
by Chiara Corti,
Luca Boscolo Bielo, Ambra Carnevale Schianca, Beatrice Taurelli Salimbeni,
Carmen Criscitiello, Giuseppe Curigliano
The Breast: VOLUME 69, P312-322, JUNE
2023 (Published: March 24, 2023)
Abstract
Metastatic breast cancer (BC) remains an incurable disease.
Besides endocrine and targeted agents, chemotherapy is still a relevant
therapeutic option for this disease. Recently, antibody-drug conjugates (ADCs)
have shown to overcome the lack of tumor specificity and systemic toxicity
typically associated with traditional chemotherapies, thus improving the
therapeutic index. To effectively exploit this technological breakthrough,
identification of optimal target antigens (Ags) is of utmost importance. To
make the ideal target, differential expression of target Ags between healthy
and cancer tissues, as well as specific mechanisms of ADC internalization after
Ag-antibody interaction are required.
Therefore, several in silico strategies to
identify and characterize new promising candidate Ags have been developed. If
initial in vitro and in vivo positive data are documented, thus providing a
biological rationale for further Ag investigation, early phase clinical trials
are designed. In BC, these strategies have already led to the development of
effective ADCs, namely trastuzumab emtansine (T-DM1), trastuzumab deruxtecan
(T-DXd) and sacituzumab govitecan (SG), primarily targeting HER2 and TROP-2.
However, promising new Ags are currently under investigation, with encouraging
results especially coming from targeting HER3, FRα, Tissue Factor, LIV-1,
ROR1-2, and B7–H4.
In this review, we describe the landscape of emergent and
future potential targets (i.e., other than HER2 and TROP-2) investigated in BC
for ADC development. Predominant target expression, function, preclinical
rationale, potential clinical implication, as well as preliminary clinical
trial results are provided.
by Isabel Blancas,
Marina Linares-Rodríguez, Eduardo Martínez de Dueñas, Carmen Herrero-Vicent,
María D. Molero-Mir, José M. Garrido, Fernando Rodríguez-Serrano
The Breast: Published: March 23, 2023
Purpose
Tamoxifen is a drug
used for hormone receptor-positive breast cancers, primarily metabolised by the
CYP2D6 enzyme into active metabolites such as endoxifen. CYP2D6 displays
varying degrees of activity depending on its genotype. This study aims to
analyse the effect of an early increase in tamoxifen dose in poor metabolisers
(PM) on survival.
Methods
We enrolled 220
patients diagnosed with breast cancer who were treated with tamoxifen. CYP2D6
polymorphisms were determined, and the phenotype was estimated according to the
Clinical Pharmacogenetics Implementation Consortium. Disease-free survival
(DFS) and overall survival (OS) were analysed considering the entire patient
group, and a subgroup of 110 patients selected by Propensity Score Matching
(PSM). All women were treated with 20 mg/day of tamoxifen for 5 years, except
PM, who initially received 20 mg/day for 4 months, followed by 40 mg/day for 4
months and 60 mg/day for 4 months before returning to the standard dose of 20
mg/day until completing 5 years of treatment.
Results
The analysis of the
influence of CYP2D6 polymorphisms in the complete group and in the PSM subgroup
revealed no significant differences for DFS or OS. Furthermore, DFS and OS were
analysed in relation to various covariates such as age, histological grade,
nodal status, tumour size, HER-2, Ki-67, chemotherapy, and radiotherapy. Only
age, histological grade, nodal status, and chemotherapy treatment demonstrated
statistical significance.
Conclusion
An early increase
in tamoxifen dose in PM patients is not associated with survival differences
among CYP2D6 phenotypes.
by Marthe Larsen,
Elsebeth Lynge, Christoph I. Lee, Kristina Lång, Solveig Hofvind
The Breast: VOLUME 69, P306-311, JUNE
2023 (Published: March 21, 2023)
Purpose
The European
Society on Breast Imaging has recommended supplemental magnetic resonance
imaging (MRI) every two to four years for women with mammographically dense
breasts. This may not be feasible in many screening programs. Also, the
European Commission Initiative on Breast Cancer suggests not implementing
screening with MRI. By analyzing interval cancers and time from screening to
diagnosis by density, we present alternative screening strategies for women
with dense breasts.
Methods
Our BreastScreen
Norway cohort included 508 536 screening examinations, including 3125
screen-detected and 945 interval breast cancers. Time from screening to
interval cancer was stratified by density measured by an automated software and
classified into Volpara Density Grades (VDGs) 1–4. Examinations with volumetric
density ≤3.4% were categorized as VDG1, 3.5%–7.4% as VDG2, 7.5%–15.4% as VDG3,
and ≥15.5% as VDG4. Interval cancer rates were also determined by continuous
density measures.
Results
Median time from
screening to interval cancer was 496 (IQR: 391–587) days for VDG1, 500 (IQR:
350–616) for VDG2, 482 (IQR: 309–595) for VDG3 and 427 (IQR: 266–577) for VDG4.
A total of 35.9% of the interval cancers among VDG4 were detected within the
first year of the biennial screening interval. For VDG2, 26.3% were detected
within the first year. The highest annual interval cancer rate (2.7 per 1000
examinations) was observed for VDG4 in the second year of the biennial
interval.
Conclusions
Annual screening of
women with extremely dense breasts may reduce the interval cancer rate and
increase program-wide sensitivity, especially in settings where supplemental
MRI screening is not feasible.
by M. Dzhugashvili,
L. Veldeman, A.M. Kirby
The Breast: VOLUME 69, P299-305, JUNE
2023 (Published:March 17, 2023)
Abstract
Given that most local relapses of breast cancer occur
proximal to the original location of the primary, the delivery of additional
radiation dose to breast tissue that contained the original primary cancer
(known as a “boost”) has been a standard of care for some decades. In the
context of falling relapse rates, however, it is an appropriate time to
re-evaluate the role of the boost. This article reviews the evolution of the
radiotherapy boost in breast cancer, discussing who to boost and how to boost
in the 2020s, and arguing that, in both cases, less is more.
Highlights
•Delivery of additional RT dose to breast tumour bed has a
sound pathological basis.
•Breast boost local relapse benefits vary according to
clinicopathological risk factors.
•Young age, high grade & triple negative phenotype are
key eligibility criteria.
•There is no survival benefit from a tumour bed boost in
breast RT.
•The boost target volume and treatment burden should be
minimised.
Thursday 2 March 2023
Breast Surgery Bulletin: March 2023
by Laura Pala,
Tommaso De Pas, Eleonora Pagan, Isabella Sala, Chiara Catania, Emma Zattarin,
Paolo Arnone, Massimo M. Grassi, Marco Colleoni, Antonio C. Wolff, Javier
Cortes, Martine Piccart, Richard D. Gelber, Giuseppe Viale, Vincenzo Bagnardi,
Fabio Conforti
The Breast: Published: March 01, 2023
Background
Controversy exists
regarding the optimal duration of the extended adjuvant endocrine treatment
(ET) in patients with early-stage breast-cancer (eBC).
We performed a
systematic review and trial-level meta-analysis of all randomized clinical
trials (RCTs) comparing a “limited-extended” adjuvant ET (defined as more than
5 but less than 7.5 years of treatment overall) versus a “full-extended”
adjuvant ET (defined as more than 7.5 years of treatment overall) in eBC.
Methods
To be eligible, RCTs
had to i) compare a “limited-extended” adjuvant ET versus a “full-extended”
adjuvant ET in patients with eBC; and ii) report disease-free survival (DFS)
hazard ratio (HR) according to the disease nodal-status [i.e., nodal-negative
(N-ve) versus nodal-positive (N + ve)].
The primary
endpoint was to assess the difference in efficacy of full-versus
limited-extended ET, measured in terms of the difference in DFS log-HR,
according to the disease nodal-status. Secondary endpoint was the difference in
efficacy of full-versus limited-extended ET according to tumor size (i.e., pT1
vs pT2/3/4), histological grade (i.e., G1/G2 vs G3), patients’ age (i.e., ≤60
vs > 60 years) and previous type of ET (i.e., aromatase inhibitors vs
tamoxifen vs switch strategy).
Results
Three phase III
RCTs fulfilled the inclusion criteria. A total of 6689 patients were included
in the analysis, of which 3506 (53%) had N + ve disease.
The full-extended
ET provided no DFS-benefit as compared with the limited-extended ET in patients
with N-ve disease (pooled DFS-HR = 1.04, 95%CI: 0.89 to 1.22; I2 = 18%).
Conversely, in
patients with N + ve disease the full-extended ET significantly
improved DFS, with a pooled DFS-HR of 0.85 (95%CI: 0.74 to 0.97; I2 = 0%).
There was a
significant interaction between the disease nodal-status and the efficacy of
the full-versus limited-extended ET (p-heterogeneity = 0.048).
The full-extended
ET provided no significant DFS-benefit as compared with the limited-extended ET
in all the other subgroups analyzed.
Conclusions
: Patients with eBC
and N + ve disease can obtain a significant DFS-benefit from the
full-extended as compared with the limited-extended adjuvant ET.
The Lancet Oncology: VOLUME
24, ISSUE 3, P273-285, MARCH 2023
Background
We aimed to report
on long-term outcomes of patients with small, node-negative, HER2-positive
breast cancer treated with adjuvant paclitaxel and trastuzumab and to establish
potential biomarkers to predict prognosis.
Methods
In this open-label,
single-arm, phase 2 study, patients aged 18 years or older, with small (≤3 cm),
node-negative, HER2-positive breast cancer, and an Eastern Cooperative Oncology
Group performance status of 0–1, were recruited from 16 institutions in 13
cities in the USA. Eligible patients were given intravenous paclitaxel (80 mg/m2)
with intravenous trastuzumab (loading dose of 4 mg/kg, subsequent doses 2
mg/kg) weekly for 12 weeks, followed by trastuzumab (weekly at 2 mg/kg or once
every 3 weeks at 6 mg/kg) for 40 weeks to complete a full year of trastuzumab.
The primary endpoint was 3-year invasive disease-free survival. Here, we report
10-year survival outcomes, assessed in all participants who received
protocol-defined treatment, with exploratory analyses using the HER2DX genomic
tool. This study is registered on ClinicalTrials.gov,
NCT00542451, and is closed to accrual.
Findings
Between Oct 29,
2007, and Sept 3, 2010, 410 patients were enrolled and 406 were given adjuvant
paclitaxel and trastuzumab and included in the analysis. Mean age at enrolment
was 55 years (SD 10·5), 405 (99·8%) of 406 patients were female and one (0·2%)
was male, 350 (86·2%) were White, 28 (6·9%) were Black or African American, and
272 (67·0%) had hormone receptor-positive disease. After a median follow-up of
10·8 years (IQR 7·1–11·4), among 406 patients included in the analysis
population, we observed 31 invasive disease-free survival events, of which six
(19·4%) were locoregional ipsilateral recurrences, nine (29·0%) were new
contralateral breast cancers, six (19·4%) were distant recurrences, and ten
(32·3%) were all-cause deaths. 10-year invasive disease-free survival was 91·3%
(95% CI 88·3–94·4), 10-year recurrence-free interval was 96·3% (95% CI
94·3–98·3), 10-year overall survival was 94·3% (95% CI 91·8–96·8), and 10-year
breast cancer-specific survival was 98·8% (95% CI 97·6–100). HER2DX risk score
as a continuous variable was significantly associated with invasive disease-free
survival (hazard ratio [HR] per 10-unit increment 1·24 [95% CI 1·00–1·52];
p=0·047) and recurrence-free interval (1·45 [1·09–1·93]; p=0·011).
Interpretation
Adjuvant paclitaxel
and trastuzumab is a reasonable treatment standard for patients with small,
node-negative, HER2-positive breast cancer. The HER2DX genomic tool might help
to refine the prognosis for this population.
by Riku Togawa,
Johanna Hederer, Moira Ragazzi, Thomas Bruckner, Sarah Fastner, Christina
Gomez, André Hennigs, Juliane Nees, André Pfob, Fabian Riedel, Benedikt
Schäfgen, Anne Stieber, Michael P. Lux, Jörg Heil, Michael Golatta
The Breast: Published: February 22, 2023
Purpose
The Histolog®
Scanner (SamanTree Medical SA, Lausanne, Switzerland) is a large field-of-view
confocal laser scanning microscope designed to allow intraoperative margin
assessment by the production of histological images ready for assessment in the
operating room. We evaluated the feasibility and the performance of the
Histolog® Scanner (HS) to correctly identify infiltrated margins in clinical
practice of lumpectomy specimens. It was extrapolated if the utilization of the
HS has the potential to reduce infiltrated margins and therefore reduce
re-operation rates in patients undergoing breast conserving surgery (BCS) due
to a primarily diagnosed breast cancer including ductal carcinoma in situ.
Methods
This is a
single-center, prospective, non-interventional, diagnostic pilot study including
50 consecutive patients receiving BCS. The complete surface of the specimen was
scanned using the HS intraoperatively. The surgery and the intraoperative
margin assessment of the specimen was performed according to the clinical
routine consisting of conventional specimen radiography as well as the clinical
impression of the surgeon. Three surgeons and an experienced pathologist
assessed the scans produced by the HS for cancer cells on the surface. The
potential of the HS to correctly identify involved margins was compared to the
results of the conventional specimen radiography alone as well as the clinical
routine. The histopathological report served as the gold standard.
Results
50 specimens
corresponding to 300 surfaces were scanned by the HS. The mean sensitivity of
the surgeons to identify involved margins with the HS was
37.5% ± 5.6%, the specificity was 75.2% ± 13.0%. The
assessment of resection margins by the pathologist resulted in a sensitivity of
37.5% and a specificity of 81.0%, while the local clinical routine resulted in
a sensitivity of 37.5% and a specificity of 78.2%.
Conclusion
Acquisition of
high-resolution histological images using the HS was feasible in clinical
practice. Sensitivity and specificity were comparable to clinical routine. With
more specific training and experience on image interpretation and acquisition,
the HS may have the potential to enable more accuracy in the margin assessment
of BCS specimens.
by Elisabeth
Solmunde, Anne Mette Falstie-Jensen, Ebbe L. Lorenzen, Marianne Ewertz, Kristin
V. Reinertsen, Olaf M. Dekkers, Deirdre P. Cronin-Fenton
The Breast: Published: February 18, 2023
Objective
Breast cancer and
breast cancer-directed radiation therapy (RT) may increase the risk of late
effects, such as hypothyroidism. We conducted a systematic review and
meta-analysis to investigate the association between breast cancer, RT, and
risk of hypothyroidism in breast cancer survivors.
Methods
Through February
2022, we searched PubMed, EMBASE, and references of relevant articles, to
identify papers on breast cancer and breast cancer-directed RT and subsequent
risk of hypothyroidism. Articles were screened by title and abstract and
reviewed for eligibility. We used a pre-formed data extraction sheet and
identified key design elements that could potentially introduce bias. The main
outcome was the confounder-adjusted relative risk (RR) of hypothyroidism in
breast cancer survivors versus women without breast cancer, and in breast
cancer survivors according to the receipt of RT to the supraclavicular lymph
nodes. We used a random-effects model to calculate pooled RRs and associated
95% confidence intervals (95% CI).
Results
From 951 papers
screened by title and abstract, 34 full-text papers were reviewed for
eligibility. We included 20 studies published between 1985 and 2021–19 were
cohort studies. Compared with women without breast cancer, the pooled RR of hypothyroidism
in breast cancer survivors was 1.48 (95% CI: 1.17, 1.87), with highest risk
associated with RT to the supraclavicular region (RR = 1.69, 95% CI:
1.16, 2.46). The most important limitations of the studies were small sample
size yielding estimates with low precision, and lack of data on potential
confounders.
Conclusion
Breast cancer and
radiation therapy to the supraclavicular lymph nodes is associated with an
increased risk of hypothyroidism.
Breast Cancer
Research volume 25,
Article number: 20 (2023)
Background
Mammography screening has been proven to detect breast
cancer at an early stage and reduce mortality; however, it has low accuracy in
young women or women with dense breasts. Blood-based diagnostic tools may
overcome the limitations of mammography. This study assessed the diagnostic
performance of a three-protein signature in patients with suspicious breast
lesions.
Findings
This trial (MAST; KCT0004847) was a prospective multicenter
observational trial. Three-protein signature values were obtained using serum
and plasma from women with suspicious lesions for breast malignancy before
tumor biopsy. Additionally, blood samples from women who underwent clear or
benign mammography were collected for the assays. Among 642 participants, the
sensitivity, specificity, and overall accuracy values of the three-protein
signature were 74.4%, 66.9%, and 70.6%, respectively, and the concordance index
was 0.698 (95% CI 0.656, 0.739). The diagnostic performance was not affected by
the demographic features, clinicopathologic characteristics, and co-morbidities
of the participants.
Conclusions
The present trial showed an accuracy of 70.6% for the
three-protein signature. Considering the value of blood-based biomarkers for
the early detection of breast malignancies, further evaluation of this
proteomic assay is warranted in larger, population-level trials.
This Multi-protein Assessment using Serum to deTermine
breast lesion malignancy (MAST) was registered at the Clinical Research
Information Service of Korea with the identification number of KCT0004847 (https://cris.nih.go.kr).
by Yitian Lang,
Qingqing Chai, Wenqi Tao, Yahui Liao, Xiaoyan Liu, Bin Wu
The Breast: Published: February 09, 2023
Purpose
The ASCENT trial
demonstrated the efficacy of sacituzumab govitecan for the treatment of advanced
or metastatic triple-negative breast cancer (TNBC). The current study evaluated
the cost-effectiveness of receiving sacituzumab govitecan compared with
standard of care chemotherapy from the United States payer perspective.
Methods
A partitioned
survival approach was used to project the disease course of advanced or
metastatic TNBC. Two survival modes were applied to analyze two groups of
patients. The survival data were gathered from the ASCENT trial. Direct medical
costs were derived from the data of Centers for Medicare & Medicaid
Services. Utility data was collected from the published literature. The
incremental cost-utility ratio (ICUR) was the primary outcome that measured the
cost-effectiveness of therapy regimen. One-way sensitivity and probabilistic
sensitivity analysis were implemented to explore the uncertainty and validate
the stability of results.
Results
In the base-case,
the ICUR of sacituzumab govitecan versus chemotherapy is $ 778,771.9/QALY and $
702,281/QALY for full population group and brain metastatic-negative (BMN)
group with the setting of classic survival mode. And in the setting of cure
survival mode, the ICUR is $ 506,504.5/QALY for the full population group and $
274,232.0/QALY for BMN population group. One-way sensitivity analyses revealed
that the unit cost of sacituzumab govitecan and body weight were key roles that
lower the ICUR value. Probabilistic sensitivity analyses also showed that
reducing the unit price of sacituzumab govitecan can improve the likelihood of
becoming cost-effective.
Conclusion
The
cost-effectiveness analysis suggested that from a US payer perspective,
sacituzumab govitecan at current price is unlikely to be a preferred option for
patients with advanced or metastatic TNBC at a threshold of $ 150,000/QALY.
by Ondine Dufour,
Gilles Houvenaeghel, Jean-Marc Classe, Monique Cohen, Christelle Faure, Chafika
Mazouni, Marie-Pierre Chauvet, Eva Jouve, Emile Darai, Anne-Sophie Azuar,
Pierre Gimbergues, Anthony Gonçalves, Alexandre de Nonneville
The Breast: Published: February 08, 2023
Background
There is a scarcity
of data exploring early breast cancer (eBC) in very young patients. We assessed
shared and intrinsic prognostic factors in a large cohort of patients aged ≤35,
compared to a control group aged 36 to 50.
Methods
Patients ≤50 were
retrospectively identified from a multicentric cohort of 23,134 eBC patients
who underwent primary surgery between 1990 and 2014. Multivariate Cox analyses
for DFS and OS were built. To assess the independent impact of age, 1 to 3
case-control analysis was performed by matching ≤35 and 36–50 years patients.
Results
Of 6481 patients,
556 were aged ≤35, and 5925 from 36 to 50. Age ≤35 was associated with larger
tumors, higher grade, ER-negativity, macroscopic lymph node involvement
(pN + macro), lymphovascular invasion (LVI), mastectomy, and
chemotherapy (CT) use. In multivariate analysis, age ≤35 was associated with
worse DFS [HR 1.56, 95% CI 1.32–1.84; p < 0.001], and OS [HR
1.29, 95% CI 1.03–1.60; p = 0.025], as were high grade, large
tumor, LVI, pN + macro, ER-negativity, period of diagnostic, and
absence of ET or CT (for DFS). Adverse prognostic impact of age ≤35 was
maintained in the case control-matched analysis for DFS [HR 1.56, 95%CI
1.28–1.91, p < 0.001], and OS [HR 1.33, 95%CI
1.02–1.73, p = 0.032]. When only considering patients ≤35, ER,
tumor size, nodal status, and LVI were independently associated with survival
in this subgroup.
Conclusions
Age ≤35 is
associated with less favorable presentation and more aggressive treatment
strategies. Our results support the poor prognosis value of young age, which
independently persisted when adjusting for other prognostic factors and
treatments.
by Manon Réda,
Anaïs Fouquier, Isabelle Desmoulins, Didier Mayeur, Courèche Kaderbhai, Silvia
Ilie, Audrey Hennequin, Bruno Coudert, Aurélie Bertaut, Sylvain Ladoire
The Breast: Published:February 04, 2023
Background
Taxanes are major
drugs for metastatic breast cancer (MBC) treatment, and are generally well
tolerated, making them attractive for therapeutic reintroduction (rechallenge)
during metastatic course. In view of the paucity of current literature, we
questioned the usefulness of taxane rechallenge in a population of patients
previously treated with taxanes in a metastatic setting.
Methods
From the local
database of a French cancer center, we retrospectively identified 756 patients
diagnosed with ER+/HER2-, or triple negative MBC, and treated between 2008 and
2021. Among them, 58 patients (7.8%) were rechallenged with taxanes. Clinical
characteristics, response rates, and survival were retrospectively evaluated
and compared to patients who received taxanes only once.
Results
Compared to
non-rechallenged population, patients treated with taxane rechallenge were
significantly younger, with better general status, and received more treatment.
First taxane exposure led to better tumor response and was more frequently
discontinued for reasons other than progression, compared to the
non-rechallenged population. Taxane rechallenge led to an objective response
rate of 27.6%, and a clinical benefit rate of 46.6%, with a median
progression-free survival (PFS) of 5.7 months, and a median overall survival
(OS) of 11.6 months. We also found a PFS2/PFS1 ratio >1.3 in 55.2% of the
rechallenge population.
Conclusion
Although only a
minority of MBC patients are concerned, taxane rechallenge appears to be a
pragmatic option with an acceptable tolerance, and good efficacy, especially
when these drugs have shown clinical activity earlier in the disease course,
and/or have been stopped for reasons other than progression.
by Eve Rodler,
Priyanka Sharma, William E Barlow, Julie R Gralow, Shannon L Puhalla, Carey K
Anders, Lori Goldstein, Debu Tripathy, Ursa A Brown-Glaberman, Thu-Tam Huynh,
Christopher S Szyarto, Andrew K Godwin, Harsh B Pathak, Elizabeth M Swisher,
Marc R Radke, Kirsten M Timms, Danika L Lew, Jieling Miao, Lajos Pusztai,
Daniel F Hayes, Gabriel N Hortobagyi
The Lancet Oncology: VOLUME
24, ISSUE 2, P162-174, FEBRUARY 2023
Background
Poly(ADP-ribose)
polymerase (PARP) inhibitors are effective in germline BRCA1 or BRCA2 (BRCA1/2) mutation-associated
metastatic breast cancer. However, studies evaluating PARP inhibitors plus
platinum-based chemotherapy in germline BRCA1/2-wildtype triple-negative
breast cancer are scarce. A large proportion of germline BRCA1/2-wildtype
triple-negative breast cancer shows homologous recombination deficiency (HRD),
resulting in a BRCA-like phenotype that might render sensitivity to PARP
inhibitors. The S1416 trial assessed the efficacy of cisplatin combined with
the PARP inhibitor veliparib in three predefined groups of metastatic breast
cancer: germline BRCA1/2-mutated, BRCA-like, and non-BRCA-like.
Methods
S1416 was a
randomised, double-blind, placebo-controlled, phase 2 trial conducted at 154
community and academic clinical sites across the USA. Eligible patients aged 18
years or older had metastatic or recurrent triple-negative breast cancer or
germline BRCA1/2-associated metastatic or recurrent breast cancer, an
Eastern Cooperative Oncology Group performance status of 0–2, and had received
up to one line of chemotherapy for metastatic disease. Patients were randomly
assigned (1:1) via the National Clinical Trials Network open interactive system
with dynamic balancing on number of previous cytotoxic regimens for metastatic
disease to receive intravenous cisplatin (75 mg/m2, day 1) combined with either
veliparib or matching placebo (300 mg orally twice a day, days 1–14) on a
21-day cycle. Investigators, patients, and the sponsors were masked to
treatment assignment; the study statisticians were unmasked. Central testing
after ran domisation classified patients as having mutated or wildtype
germline BRCA1/2. A biomarker panel established a priori was used to
classify patients with wildtype germline BRCA1/2 into BRCA-like and
non-BRCA-like phenotype groups, with BRCA-like status based on at least one of the
biomarkers: genomic instability score (≥42), somatic BRCA1/2 mutations, BRCA1 promoter
methylation, or non-BRCA1/2 homologous recombination repair germline
mutations. The primary endpoint was investigator-assessed progression-free
survival, analysed separately for the three predefined biomarker groups with a
prespecified α value for each analysis. Efficacy analyses were done by
intention to treat and included all eligible patients. Safety analyses of
toxicities attributed to treatment included all patients who received at least
one dose of veliparib or placebo. The study is ongoing and registered
with ClinicalTrials.gov,
NCT02595905.
Findings
Between July 7,
2016, and June 15, 2019, 335 patients were enrolled and randomly assigned. 320
patients (n=162 to cisplatin plus veliparib, all women; and n=158 to cisplatin
plus placebo, 157 women and one man) were eligible for efficacy evaluation. 247
patients were classified into the three biomarker groups: germline BRCA1/2-mutated
(n=37), BRCA-like (n=101), and non-BRCA-like (n=109). 73 patients could not be
classified due to missing biomarker information. Median follow-up was 11·1
months (IQR 5·6–20·8). In the germline BRCA1/2-mutated group, median
progression-free survival was 6·2 months (95% CI 2·3–9·2) in the cisplatin plus
veliparib group and 6·4 months (4·3–8·2) in the cisplatin plus placebo group
(HR 0·79 [95% CI 0·38–1·67]; log-rank p=0·54). In the BRCA-like group, median
progression-free survival was 5·9 months (95% CI 4·3–7·8) in the cisplatin plus
veliparib group versus 4·2 months (2·3–5·0) in the cisplatin plus placebo group
(HR 0·57 [95% CI 0·37–0·88]; p=0·010). In the non-BRCA-like group, median
progression-free survival was 4·0 months (95% CI 2·5–4·7) in the cisplatin plus
veliparib group versus 3·0 months (2·2–4·4) in the cisplatin plus placebo group
(HR 0·89 [95% CI 0·60–1·33]; p=0·57). The most common grade 3 or worse adverse
events attributed to treatment were neutropenia (71 [46%] of 155 patients in
the cisplatin plus veliparib group vs 29 [20%] of 147 in the
cisplatin plus placebo group), leukopenia (42 [27%] vs 11 [7%]),
anaemia (35 [23%] vs 12 [8%]), and thrombocytopenia (29 [19%] vs four
[3%]). Serious adverse events attributed to treatment occurred in 48 (31%)
patients in the cisplatin plus veliparib group and 53 (36%) patients in the
cisplatin plus placebo group. Treatment-related adverse events led to death in
one patient in the cisplatin plus veliparib group (sepsis) and one patient in
the cisplatin plus placebo group (acute kidney injury due to cisplatin plus
heart failure from previous doxorubicin exposure).
Interpretation
The addition of
veliparib to cisplatin significantly improved progression-free survival in
patients with BRCA-like metastatic triple-negative breast cancer, but not in
patients with non-BRCA-like metastatic breast cancer. PARP inhibitors combined
with platinum-based chemotherapy should be explored further in BRCA-like
triple-negative breast cancer.
Thursday 2 February 2023
Breast Surgery Bulletin: Feb 2023
by Carolyn Ee,
Adele Cave, Vaishnavi Vaddiparthi, Dhevaksha Naidoo, John Boyages
The Breast: Published: January 25, 2023
Purpose
Weight gain after
breast cancer is common. The aim of this study was to determine factors
associated with weight gain after breast cancer in Australian women.
Methods
A cross-sectional
online survey was conducted between November 2017 and January 2018. Women
living in Australia who self-identified as having breast cancer or ductal
carcinoma in-situ were eligible. We created stepwise linear and logistic
regression models to evaluate predictors for absolute and clinically
significant (≥5%) weight gain respectively.
Results
Data from 276 women
were analysed. Most were Caucasian and 92% had been diagnosed with Stage 0-III
breast cancer. Absolute weight gain was associated with hot flushes, being in
the menopausal transition at diagnosis, being less physically active than at
diagnosis, lower eating self-efficacy when watching television or using a
computer, and higher self-efficacy when anxious or nervous
(F-ratio = 3.26, R2-adjusted = 0.16, p < .001).
Clinically significant weight gain was associated with tamoxifen use (OR 2.7),
being less physically active than at diagnosis (OR 3.1), and lower eating
self-efficacy when watching television or using a computer (OR 0.82)
(Chi-square 64.94, df = 16, p < .001). Weight
gain was not associated with chemotherapy, radiotherapy, aromatase inhibitor
use, number of lymph nodes removed, or body mass index at diagnosis.
Conclusions
Interventions to
prevent weight gain after breast cancer, particularly aiming to maintain
physical activity, should be targeted at women receiving tamoxifen. The role of
eating self-efficacy, especially attentive eating, in managing weight after
breast cancer should be explored.
Axillary lymph node dissection: Dead or still alive?
by Anna C. Beck,
Monica Morrow
The Breast: Published: January 23, 2023
Highlights
·
Axillary surgery in BC has been de-escalated for
a significant group of patients, but an ALND is still necessary for some
·
ALND remains necessary for staging in patients
where SLNB has not been demonstrated to be accurate
·
This includes patients with clinically palpable
lymph nodes and patients with cT4 or cN2-3 disease
·
ALND is required for local control in patients
with a heavy axillary tumor burden and recurrent axillary disease
·
Use of newer systemic therapy may require
complete axillary staging with ALND to determine eligibility for use.
Abstract
Although sentinel lymph node biopsy is now the primary
method of axillary staging and is therapeutic for patients with limited nodal
disease, axillary lymph node dissection (ALND) is still necessary for staging
in groups where sentinel lymph node biopsy has not been proven to be accurate
and to maintain local control in those with a heavy axillary tumor burden.
Additionally, newer approaches to systemic therapy tailored to risk level
sometimes necessitate knowledge of the number of involved axillary nodes which
can only be obtained with ALND. Ongoing trials will address whether there are
additional circumstances where radiotherapy can replace ALND.
by André Pfob,
Peter Dubsky
The Breast: Published: January 17, 2023
Abstract
Breast conserving therapy (BCT), consisting of breast
conserving surgery and subsequent radiotherapy, is an equivalent option to
mastectomy for women with early breast cancer. Although BCT after neoadjuvant
systemic treatment (NAST) has been routinely recommend by international
guidelines since many years, the rate of BCT worldwide varies largely and its
potential is still underused. While the rate of BCT in western countries has
increased over the past decades to currently about 70%, the rate of BCT is as low
as 10% in other countries. In this review, we will evaluate the underused
potential of breast conservation after NAST, identify causes, and discuss
possible solutions. We identified clinical and non-clinical causes for the
underuse of BCT after NAST including uncertainties within the community
regarding oncologic outcomes, the correct tumor localization after NAST, the
management of multifocal and multicentric tumors, margin assessment,
disparities of socio-economic aspects on a patient and national level, and
psychological biases affecting the shared decision-making process between
patients and clinicians. Possible solutions to mitigate the underuse of BCT
after NAST include interdisciplinary teams that keep the whole patient pathway
in mind, optimized treatment counseling and shared decision-making, and
targeted financial support to alleviate disparities.
by Thibaut
Sanglier, Jinjoo Shim, Neil Lamarre, Claudia Peña-Murillo, Vincent Antao,
Filippo Montemurro
The Breast: Published: January 15, 2023
Background
Trastuzumab
emtansine (T-DM1) has demonstrated improvements in survival and neurological
symptoms in patients with breast cancer with brain metastases (BCBM). This
real-world study investigated the effectiveness of T-DM1 versus lapatinib plus
capecitabine (LC) in patients with BCBM.
Methods
This retrospective,
observational study evaluated patients with HER2–positive BCBM using a
real-world database. Eligible patients had initiated T-DM1 or LC with a prior
diagnosis of brain metastasis and ≥1 prior metastatic breast cancer treatment.
The primary endpoint was overall survival (OS); secondary endpoints were time
to next relevant treatment or death (TTNT) and real-world progression-free
survival (rwPFS). An inverse probability of treatment weighting (IPTW) approach
was used to account for differences in potential baseline characteristics
between treatment groups. Outcomes were described using the Kaplan-Meier
method, and the average treatment effect of initiating T-DM1 versus LC was
estimated using weighted Cox proportional hazard models and hazard ratio (HR).
Results
A total of 214
patients were available for analysis (T-DM1, n = 161; LC,
n = 53). Demographics and baseline characteristics were generally
well-balanced between treatment groups after weighting. After weighting, median
OS was 17.7 (T-DM1) versus 9.6 (LC) months (HR, 0.55 [95% CI, 0.34–0.89]; P=0.013).
Median TTNT was 9.0 (T-DM1) versus 6.0 (LC) months (HR, 0.55 [95% CI,
0.36–0.85]; P = 0.005). After weighting, median rwPFS was 6.0
(T-DM1) versus 4.0 (LC) months (HR, 0.50 [95% CI, 0.36–0.69]; P < 0.001).
Conclusions
These results
support the superior effectiveness and clinical relevance of T-DM1 versus LC in
patients with HER2-positive BCBM in the real world.
How I treat HER2-low advanced breast cancer
by Ilana Schlam,
Sara M. Tolaney, Paolo Tarantino
The Breast: Published: January 11, 2023
Introduction
Targeting low
levels of human receptor epidermal growth factor 2 (HER2) expression has
reshaped the treatment paradigm for half of the patients with advanced breast
cancer. HER2-low is currently defined as a HER2 immunohistochemical expression
of 1+ or 2+ without amplification by in-situ hybridization. Until recently, HER2-targeted
agents were ineffective in treating patients with HER2-low disease.
Areas covered
In this narrative
review, we summarize the current management of HER2-low breast cancer. We
highlight the findings of the DESTINY-Breast 04 phase 3 trial, which confirmed
the efficacy of trastuzumab-deruxtecan (T-DXd) for the treatment of patients
with advanced, pretreated HER2-low breast cancer. We also discuss how to
implement this new treatment option in treatment algorithms of hormone receptor
(HR)-positive and triple-negative tumors, as well as how to optimally manage
selected toxicities of T-DXd.
Expert opinion
T-DXd is currently
the standard of care for patients with advanced, pretreated, HER2-low breast
cancer. Based on the design of the DESTINY-Breast04 trial, the current optimal
place in treatment algorithms is after the first line of chemotherapy, both in
HR-positive and triple-negative breast cancer. Up to 10–15% of the patients
receiving T-DXd are expected to develop interstitial lung disease, which in 1–2%
of the cases can be fatal. Adequate monitoring and prompt management are
required to minimize the impact of ILD and to safely implement T-DXd in
clinical practice.
Polygenic risk scores and breast cancer risk prediction
by Eleanor Roberts,
Sacha Howell, Gareth Evans
The Breast: VOLUME 67, P71-77, FEBRUARY
2023
Abstract
Polygenic Risk Scores (PRS) are a major component of
accurate breast cancer risk prediction and have the potential to improve
screening and prevention strategies. PRS combine the risk from Single
nucleotide polymorphisms (SNPs) associated with breast cancer in Genome Wide
Association Studies (GWAS) and explain over 30% of breast cancer heritability.
When incorporated into risk models, the more personalised risk assessment
derived from PRS, help identify women at higher risk of breast cancer
development and enables the implementation of stratified screening and
prevention approaches. This review describes the role of PRS in breast cancer
risk prediction including the development of PRS and their clinical
application. We have also examined the role of PRS within more well-established
risk prediction models which incorporate known classic risk factors and discuss
the interaction of PRS with these factors and their capacity to predict breast
cancer subtypes. Before PRS can be implemented on a population-wide scale,
there are several challenges that must be addressed. Perhaps the most pressing
of these is the use of PRS in women of non-White European origin, where PRS
have been shown to have attenuated risk prediction both in discrimination and
calibration. We discuss progress in developing and applying PRS in non-white
European populations. PRS represent a significant advance in breast cancer risk
prediction and their further development will undoubtedly enhance
personalisation.
Omission of axillary sentinel lymph node biopsy in early
invasive breast cancer
by Toralf Reimer
The Breast: Published: January 09, 2023
Abstract
A systematic review of the impact of the COVID-19 pandemic on
breast cancer screening and diagnosis
by Tong Li,
Brooke Nickel, Preston Ngo, Kathleen McFadden, Meagan Brennan, M Luke
Marinovich, Nehmat Houssami
The Breast: VOLUME 67, P78-88, FEBRUARY
2023
Background
Breast cancer care
has been affected by the COVID-19 pandemic. This systematic review aims to
describe the observed pandemic-related changes in clinical and health services
outcomes for breast screening and diagnosis.
Methods
Seven databases
(January 2020–March 2021) were searched to identify studies of breast cancer
screening or diagnosis that reported observed outcomes before and related to
the pandemic. Findings were presented using a descriptive and narrative
approach.
Results
Seventy-four
studies were included in this systematic review; all compared periods before
and after (or fluctuations during) the pandemic. None were assessed as being at
low risk of bias. A reduction in screening volumes during the pandemic was
found with over half of studies reporting reductions of ≥49%. A majority (66%)
of studies reported reductions of ≥25% in the number of breast cancer
diagnoses, and there was a higher proportion of symptomatic than
screen-detected cancers. The distribution of cancer stage at diagnosis during
the pandemic showed lower proportions of early-stage (stage 0–1/I-II, or Tis
and T1) and higher proportions of relatively more advanced cases than that in
the pre-pandemic period, however population rates were generally not reported.
Conclusions
Evidence of
substantial reductions in screening volume and number of diagnosed breast
cancers, and higher proportions of advanced stage cancer at diagnosis were
found during the pandemic. However, these findings reflect short term outcomes,
and higher-quality research examining the long-term impact of the pandemic is
needed.
[Clinical Picture] Chest mass in a transgender man after top
surgery
by Chandler S
Cortina, Amanda L Kong
The Lancet
Oncology CLINICAL PICTURE| VOLUME
24, ISSUE 1, E57, JANUARY 2023
A 37-year-old
transgender man presented to the outpatient Breast Care Clinic at the Medical
College of Wisconsin (WI, USA) for evaluation of a new left chest mass in
April, 2022, which he had noticed 1 month earlier. The mass was painless, and
he had no other symptoms. His previous surgical history was notable in that he
had undergone chest masculinisation surgery, colloquially called top surgery, 5
years earlier and was on gender-affirming testosterone therapy for the past 10
years. His family history was significant for a mother who had passed away from
breast cancer in her 20s and a sister who was recently diagnosed with breast
cancer at age 39 years.
by Stephen R D
Johnston, Masakazu Toi, Joyce O'Shaughnessy, Priya Rastogi, Mario Campone,
Patrick Neven, Chiun-Sheng Huang, Jens Huober, Georgina Garnica Jaliffe, Irfan
Cicin, Sara M Tolaney, Matthew P Goetz, Hope S Rugo, Elzbieta Senkus, Laura
Testa, Lucia Del Mastro, Chikako Shimizu, Ran Wei, Ashwin Shahir, Maria Munoz,
Belen San Antonio, Valérie André, Nadia Harbeck, Miguel Martin, monarchE
Committee Members
The Lancet Oncology: VOLUME 24,
ISSUE 1, P77-90, JANUARY 2023
Background
Adjuvant
abemaciclib plus endocrine therapy previously showed a significant improvement
in invasive disease-free survival and distant relapse-free survival in hormone
receptor-positive, human epidermal growth factor receptor 2 (HER2; also known
as ERBB2)-negative, node-positive, high-risk, early breast cancer. Here, we
report updated results from an interim analysis to assess overall survival as
well as invasive disease-free survival and distant relapse-free survival with
additional follow-up.
Methods
In monarchE, an
open-label, randomised, phase 3 trial, adult patients (aged ≥18 years) who had
hormone receptor-positive, HER2-negative, node-positive, early breast cancer at
a high risk of recurrence with an Eastern Cooperative Oncology Group
performance status of 0 or 1 were recruited from 603 sites including hospitals
and academic and community centres in 38 countries. Patients were randomly
assigned (1:1) by means of an interactive web-based response system (block size
of 4), stratified by previous chemotherapy, menopausal status, and region, to
receive standard-of-care endocrine therapy of physician's choice for up to 10
years with or without abemaciclib 150 mg orally twice a day for 2 years
(treatment period). All therapies were administered in an open-label manner
without masking. High-risk disease was defined as either four or more positive
axillary lymph nodes, or between one and three positive axillary lymph nodes
and either grade 3 disease or tumour size of 5 cm or larger (cohort 1). A
smaller group of patients were enrolled with between one and three positive
axillary lymph nodes and Ki-67 of at least 20% as an additional risk feature
(cohort 2). This was a prespecified overall survival interim analysis planned to
occur 2 years after the primary outcome analysis for invasive disease-free
survival. Efficacy was assessed in the intention-to-treat population. Safety
was assessed in all treated patients. The study is registered with ClinicalTrials.gov, NCT03155997, and is
ongoing.
Findings
Between July 17,
2017, and Aug 12, 2019, 5637 patients were randomly assigned (5601 [99·4%] were
women and 36 [0·6%] were men). 2808 were assigned to receive abemaciclib plus
endocrine therapy and 2829 were assigned to receive endocrine therapy alone. At
a median follow-up of 42 months (IQR 37–47), median invasive disease-free
survival was not reached in either group and the invasive disease-free survival
benefit previously reported was sustained: HR 0·664 (95% CI 0·578–0·762,
nominal p<0·0001). At 4 years, the absolute difference in invasive
disease-free survival between the groups was 6·4% (85·8% [95% CI 84·2–87·3] in
the abemaciclib plus endocrine therapy group vs 79·4% [77·5–81·1] in
the endocrine therapy alone group). 157 (5·6%) of 2808 patients in the abemaciclib
plus endocrine therapy group died compared with 173 (6·1%) of 2829 patients in
the endocrine therapy alone group (HR 0·929, 95% CI 0·748–1·153; p=0·50). The
most common grade 3–4 adverse events were neutropenia (in 548 [19·6%] of 2791
patients receiving abemaciclib plus endocrine therapy vs 24 [0·9%] of
2800 patients in the endocrine therapy alone group), leukopenia (318
[11·4%] vs 11 [0·4%]), and diarrhoea (218 [7·8%] vs six
[0·2%]). Serious adverse events occurred in 433 (15·5%) of 2791 patients
receiving abemaciclib plus endocrine therapy versus 256 (9·1%) of 2800
receiving endocrine therapy. There were two treatment-related deaths in the
abemaciclib plus endocrine therapy group (diarrhoea and pneumonitis) and none
in the endocrine therapy alone group.
Interpretation
Adjuvant
abemaciclib reduces the risk of recurrence. The benefit is sustained beyond the
completion of treatment with an absolute increase at 4 years, further
supporting the use of abemaciclib in patients with high-risk hormone receptor-positive,
HER2-negative early breast cancer. Further follow-up is needed to establish
whether overall survival can be improved with abemaciclib plus endocrine
therapy in these patients.
Wednesday 4 January 2023
Breast Surgery Bulletin: December 2022
by Gauthier
Glemarec, Jean Louis Lacaze, Bastien Cabarrou, Richard Aziza, Eva Jouve,
Slimane Zerdoud, Eleonora De Maio, Carole Massabeau, Maxime Loo, Vincent
Esteyrie, Mony Ung, Florence Dalenc, Francoise Izar, Ciprian Chira
The Breast: Published: December 29, 2022
Purpose
Local ablative
treatment (LAT) is increasingly combined with systemic therapy in
oligometastatic breast cancer (OMBC), without a high-level evidence to support
this strategy. We evaluated the addition of LAT to systemic treatment in terms
of progression-free survival (PFS) and overall survival (OS). Secondary
endpoints were local control (LC) and toxicity. We sought to identify
prognostic factors associated with longer OS and PFS.
Methods and
materials
We identified
consecutive patients treated between 2014 and 2018 for synchronous or
metachronous OMBC (defined as ≤ 5 metastases). LAT included stereotactic body
(SBRT) and volumetric modulated arc therapy (VMAT), surgery, cryotherapy and
percutaneous radiofrequency ablation (PRA). PFS and OS were calculated and Cox
regression models analyzed for potential predictors of survival.
Results
One hundred two
patients were included (no-LAT, n = 62; LAT, n = 40). Sixty-four metastases
received LAT. Median follow-up was 50.4 months (95% CI [44.4; 53.4]). One
patient experienced grade 3 toxicity in the LAT group. Five-year PFS and OS
were 34.75% (95% CI [24.42–45.26]) and 63.21% (95% CI [50.69–73.37])
respectively. Patients receiving both LAT and systemic therapy had longer PFS
and OS than those with no-LAT ([HR 0.39, p = 0.002]) and ([HR 0.31, p = 0.01]).
The use of LAT, HER2-positive status and hormone-receptor positivity were
associated with longer PFS and OS whereas liver metastases led to worse PFS.
Conclusions
LAT was associated
with improved outcomes in OMBC when added to systemic treatment alone, without
significantly increasing toxicity. The prognostic factors identified to extend
PFS and OS may help guide clinicians in selecting patients for LAT.
by E.L. Meier, D.R.
Mink van der Molen, C.A. Lansdorp, M.C.T. Batenburg, F. van der Leij, H.M.
Verkooijen, O. Boonstra, S. Hummelink, D.J.O. Ulrich
The Breast: Published: December 22, 2022
Purpose
This systematic
review aims to provide an overview of the literature on the effect of
hyperbaric oxygen therapy (HBOT) on symptoms of local late radiation toxicity
(LRT) in patients treated for breast cancer.
Methods
A systematic search
was performed in September 2021. All studies with a sample size of ≥10 patients
reporting the effect of HBOT for symptoms of LRT after radiotherapy of the
breast and/or chest wall were included. The ROBINS-I tool was used for critical
appraisal of methodological quality. The toxicity outcomes pain, fibrosis,
lymphedema, necrosis/skin problems, arm and shoulder mobility, and breast and
arm symptoms were evaluated.
Results
Nine studies
concerning a total of 1308 patients were included in this review. Except for
one study, sample sizes were small. Most studies had inadequate methodology
with a substantial risk of bias. Post-HBOT, a significant reduction of pain was
observed in 4/5 studies, of fibrosis in 1/2 studies, and of lymphedema of the
breast and/or arm in 4/7 studies. Skin problems of the breast were
significantly reduced in 1/2 studies, arm- and shoulder mobility significantly
improved in 2/2 studies, and breast- and arm symptoms were significantly
reduced in one study.
Conclusion
This systematic
review indicates that HBOT might be useful for reducing symptoms of LRT in
breast cancer patients, however evidence is limited. A randomized controlled
trial in a larger cohort of patients including a combination of patient- and
clinician-reported outcome measures would be valuable to assess the effect of
HBOT on symptoms of LRT.
Adjuvant chemotherapy for resected triple negative breast
cancer patients: A network meta-analysis
by Fausto Petrelli,
Valentina Bertaglia, Maria Chiara Parati, Karen Borgonovo, Pushpamali De Silva,
Andrea Luciani, Silvia Novello, Mario Scartozzi, Leisha A. Emens, Cinzia
Solinas
The Breast: Published: December 15, 2022
Abstract:
The current standard of care for resected early-stage triple
negative breast cancer (TNBC) patients who did not receive systemic
preoperative therapy is adjuvant anthracycline- and taxane-based chemotherapy
(CT). A network meta-analysis (NMA) of randomized controlled trials (phase III)
enrolling patients with resected stage I-III TNBC comparing adjuvant regimens
was performed. Overall survival (OS) and disease-free survival (DFS) data were
extracted. A total of 27 phase III clinical trials were selected including
15,242 TNBC patients. This NMA showed an OS benefit from the incorporation of
capecitabine into classic anthracycline/taxane-based combinations compared to
anthracyclines with or without taxanes alone.
Highlights:
·
The current adjuvant therapy for resected
early-stage triple negative breast cancer is adjuvant chemotherapy.
·
A network meta-analysis (NMA) of randomized
controlled trials was performed.
·
A total of 27 phase III clinical trials were
selected including 15,242 TNBC patients.
·
Anthracycline- and taxane-plus
capecitabine-based CT resulted in better OS than other regimens.
·
Similarly capecitabine-based triplets and the
carboplatin/paclitaxel doublet ranked the best for DFS.