Contemporary Management of Early

Breast Cancer
What’s New?
Part 3- Neoadjuvant Strategy
Dr Mastura Md Yusof
Consultant Clinical Oncologist
March 2023
 Prior Rationale for Neoadjuvant Systemic Therapy

Historically the indication was for downstaging of locally advanced breast cancer
rendering it “operable”

and to facilitate
breast conservation
surgery

mastectomy • Smaller lumpectomy

mastectomy and recon • Deescalating axillary surgery
 Current Rationale for Neoadjuvant Systemic Therapy in high risk or
locally advanced eBC
Even though the cancer is operable upfront, neoadjuvant systemic treatment (NST) which is the
administration of systemic therapy, either chemotherapy, anti HER2 therapy, immunotherapy or
endocrine therapy, prior to definitive breast surgery could be the preferred standard option

Early initiation of Strategising and optimizing

further treatment Improve breast
systemic therapy conserving rate
to improve overall versus
The pattern of response to
survival (OS) by mastectomy
NST is used to tailor systemic
eliminating micro and locoregional treatment,
metastases… that is, to escalate treatment
in non-responders and de-
escalate treatment in
responders.
 Contemporary Rationales for Neoadjuvant therapy

1. Provides effective Diagnosis

systemic treatment

Prevent cancer recurrence and

improve survival (eliminate Neaodjuvant
systemic therapy Primary surgery
micrometases early)
Enable a rapid assessment of
clinical response
Adjuvant
Surgery treatment to
eliminate
micrometastases
Provide individualised post-
treatment prognostic
information (e.g.pCR, residual PCR Non PCR
cancer burden)

Allows optimization of Deescalate Escalate adjuvant

management adjuvant therapy therapy
 Contemporary Rationales for Neoadjuvant therapy

2. Deescalating surgical procedures

diagnosis

Neaodjuvant
systemic Mastectomy
therapy

Render tumour
operable and Breast
Breast
Conserving
allow BCS Conserving Surgery and AC
Surgery

Provide time for germline

mutation test results (BRCA,
Turning AC to SLNB SLNB PALB2 etc) that may
influence surgical plans in
pts suspected to have
hereditary cancers.
 Neoadjuvant Versus Adjuvant Systemic Treatment in Breast Cancer: The Early
Breast Cancer Trialists’ Collaborative Group (EBCTCG) meta-analysis
Conclusion : NO
statistically or
clinically significant
difference in terms
of death, disease
progression, or
distant disease
recurrence betw
neoadjuvant
chemotherapy
therapy and
adjuvant therapy

Caveats
• Older regimens
• Mixed tumour
subtypes

J Natl Cancer Inst. 2005;97(3):188-194. doi:10.1093/jnci/dji021

 Huge and Newer prospective database study showing that
breast conservation may lead to greater survival.

Overall and
breast
cancer–
specific
relative
survival gain
of 56% to
70% in node-
negative
patients.
JAMA Surg. 2021;156(7):628-637. doi:10.1001/jamasurg.2021.1438
NSABP -18:
Neoadjuvant Chemotherapy increases breast conservation rate
 Landmark studies also suggest that NACT is as good as adjuvant CT
and some studies showed improved event-free survival (EFS) and Overall Survival after PCR

A particular group of patients in Pooled analysis of 12 neoadjuvant chemotherapy trials ( n=11,955):

the NACT arm that experience a
superior survival result- those who
had a pathologic complete
response (pCR) in their removed
tumour after the neoadjuvant
therapy

Pathologic Complete Response (pCR) is

defined as complete disappearance of
any invasive cancer cells in the excised
breast tissue and lymph nodes after
the end of the neo adjuvant systemic
therapy (ypT0/Tis, ypN0).

Cortazar P et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis Lancet. 2014;
NAST : Periodic clinical and Radiological Assessment of Tumour Response
• Prior to each cycle of chemotherapy, a physical examination
should be performed to monitor response to therapy

Proceed to surgery earlier

Pre Neoadjuvant Marking of tumour location

• At the conclusion of therapy, repeat breast imaging including a mammogram and
ultrasound may be performed
Summary : Advantages of Neoadjuvant Therapy in HER2+ eBC

Improve
Achieving a outcome in Obtain tumoral The presence of
pathologic patients with shrinkage -
increase the residual disease
complete high risk of
metastases chances of after
response after surgical resection neoadjuvant
neoadjuvant therapy
treatment is indicates the
associated with existence of
improved partial
Enable Tailor adjuvant
prognosis in treatment
in vivo therapy according
breast cancer to tumour resistance in the
assessment of
tumour response response tumour
(pCR) : (ypT0, ypN0).
 Which breast cancer patients
will derive the most clinical benefit from
neoadjuvant therapy?

high-risk breast tumours

Grade 3
• Triple negative
• HER2 positive
• Locally advanced cancers – T3/T4 or node positive
• BRCA 1&2 carriers

• And younger age

Which HER2 Positive or TNBC patients that do not require neoadjuvant
therapy prior to surgery?

Stage 1 ( 1-2cm) HER2 positive Stage 1 ( > 0.5- 2 cm) TNBC

• Primary surgery is standard • Primary surgery is standard
• Followed by Adjuvant therapy • Followed by Adjuvant therapy
– Chemotherapy – Chemotherapy
– Trastuzumab – Radiotherapy
– Radiotherapy
 Trastuzumab concurrent with chemotherapy or sequential to chemotherapy consistently
showed better Disease Free Survival and Overall Survival Rates
Study n/med FU study type DFS OS References

BCIRG 006 3222/5 years HR 0.64, p < 0.001; 75% versus HR 0.63, p < 0.001; HR 0.77, p = Slamon et al
84% versus 81% 0.04 (2011)
• 87% vs 92% vs 91%
FINHER 232/5.1 years HR 0.65, p = 0.12 HR 0.55, p = 0.09 Joensuu et al
• 73.3% versus 80.9% • 82.3% versus 91.3% (2006)

NCCTG N9831 4046/8.4 years concurrent HR 0.60, p < 0.001 HR 0.63, p < 0.001 Perez et al
and NSABP B— • 62.3% versus 73.7% • 75.2% versus 84.0% (2014)
31
APT 406/7 years 93.3% 95% Tolaney et al.

NCCTG N9831 2184/6 years HR 0.69, p < 0.001 • HR 0.88, p < 0.343 Perez et al
trial • 71.8% versus 80.1% • 88.4% versus 89.3% (2011)

FNCLCC— 3010/3 years HR 0.86, p = 0.41 R 1.27, p = NR Spielmann et al

sequential
PACS04 trial • 77.9% versus 80.9% • 96% versus 95% (2009)
arm

HERA 3401/11 years HR 0.76, p < 0.001 HR 0.85, p < 0.11 .Gianni et al
• 72.2% versus 78.6% • 87.7% versus. 89.3% (2011)
Ecancermedicalscience. 2015; 9: 523.
 Adjuvant antiHEr2
• The addition of anti-HER2 therapy (mainly trastuzumab and pertuzumab) to chemotherapy has
changed the natural history of this disease.
• Continuing trastuzumab for up to 1 year substantially improves overall survival (HR 0·63, 0·54–0·73;
p<0·001),
• Concurrent administration of trastuzumab with the taxane seems more effective than sequential
therapy ( cheno then trastuzumab)
• Duration of trastuzumab therapy in patients with early breast cancer remains at 1 year total.
– The data on shorter duration of antiHEr2 therapy has been mixed and are still controversial.
PERSEPHONE trial demonstrated non-inferiority of 6 months of trastuzumab compared with 12
months for patients receiving anthracycline–taxane, whereas the results of the PHARE, SOLD and
HORG trials did not show non-inferiority of treatment for 6 months versus 12 months. This shorter
durations can be considered in countries with low resources, to allow more women to benefit to a
slightly lower extent
– Longer than 1 year of duration is no more effective, as demonstrated by the HERA trial
• The therapy benefit of adjuvant trastuzumab is independent of tumour size. All benefit
• Nevertheless, ( de-escalation) of treatment in patients with lower risk such as in node-negative
patients with tumour diameters up to 3 cm, was attempted at in the APT regimen giving 12 times
weekly paclitaxel plus trastuzumab. Excellent 3-year invasive disease- free survival of 98·7% (95% CI
97·6–99·8) was obtained and this regimen becomes an option for this low-risk group.
 Despite the successes of adjuvant trastuzumab after concurrent chemo-trastuzumab in
Her2 + eBC,
Risk of relapse is consistently seen on long term follow up and BC recurrence is the most
frequent cause of death in adjuvant trastuzumab trials

courtesy of Dr Shaheenah Dawood

 How can we improve on HER2 positive EBC overall outcome?

Can we prevent recurrence and improve

survival further?
PCR, IDFS

Can we tailor the adjuvant therapy

according to tumour response ?
In locally advanced TDM-1 in non PCR
cancers
Can we tailor sequence of therapy
according to nodal positive status, ER
In resectable HER2 positive eBC with status
good cosmetic outcome to the breast
Can we deescalate surgery to the axilla?
 Dual Anti HER2 with pertuzumab and trastuzumab
in High Risk HER2+ EBC was tested

The trial found that pertuzumab, when added to chemotherapy and trastuzumab, significantly improved the
rates of invasive-disease free survival among patients with HER2-positive early breast cancer. Pertuzumab
was associated with more toxic effects than placebo — mainly low-grade diarrhea
 In patients who only had trastuzumab adjuvant and has completed one
year treatment, iDFs with the addition of neratinib, an aoral TKI was tested in the
ExteNET study : Neratinib in the extended ‘post-adjuvant’ setting
Neratinib x 1 year
Adjuvant trastuzumab 240 mg/day
+ chemotherapy

ExteNET1 1 Standard adjuvant Study post-adjuvant

Surgery therapy
R therapy
IDFS

Adjuvant
studies2,3 Surgery R Study adjuvant therapy DFS/IDFS

• Primary endpoint:1 IDFS at 2 years

• Secondary endpoints:1 DFS-DCIS, time to distant recurrence, distant DFS, CNS
metastases, overall survival, safety
• Other analyses:1 Biomarkers, health outcome assessment (FACT-B, EQ-5D)
• Stratified by:1 Nodes 0, 1–3 vs. 4+, ER/PR status, concurrent vs. sequential
trastuzumab 1. Chan A, et al. Lancet Oncol 2016; 17:367–377;
2. Goldhirsch A, et al. Lancet 2013; 382:1021–1028;
DCIS, ductal carcinoma in situ. 3. von Minckwitz G, et al. Cancer Res 2011;71(24 Suppl):Abstract OT1-02-04. 19
Conclusions for EXTENET : in patients who had already received 1 year of trastuzumab, an
additional 1 year of neratinib (versus placebo) improved invasive DFS with the effect being most
pronounced in in hormone receptor-positive, HER2-positive disease (HR 0.73; 95% CI 0.57–0.92, P
= 0.0083)
However, the additional value of neratinib in the context of after adjuvant dual blockade with
pertuzumab trastuzumab or or post-neoadjuvant T-DM1 is not clear.
 HER2-positive early breast cancer
a shift towards neoadjuvant strategy
• The vast majority of patients with a tumour of 2 cm or larger or nodal involvement receive
neoadjuvant trastuzumab plus pertuzumab, in addition to either
– doxorubicin–cyclophosphamide followed by a taxane
– epirubicin cyclophosphamide followed by a taxane
– docetaxel–carboplatin
• This regimen increased the pathological complete response rate to about 65–70% and led to an
improvement in event-free survival and disease-free survival over just giving standard neoadjuvant
chemotherapy
• Questions : In resectable HER2-positive eBC with good cosmetic outcome to the breast
– Can we prevent recurrence and improve survival further? PCR, IDFS
– Can we tailor the adjuvant therapy according to tumour response ? TDM-1 in non PCR
– Can we tailor sequence of therapy according to nodal positive status, ER status?
– Can we de-escalate surgery to the axilla?
NOAH : Neoadjuvant Trastuzumab plus Chemotherapy

Adding Transtuzumab to NACT

• Higher no of pCR (45 vs 23)
• Higher pCR is ass. better event free survival (recurrence, distant mets) & OS
• But effect is absent without achieving pCR despite adding trastuzumab
 TRYPHAENA
Trastuzumab plus pertuzumab and Carboplatin Taxane

The findings by neoSPHERE were further supported by the high pCR rates observed in
TRYPHAENA
This supports usage on non anthracycline based CT used in this neoadjuvant regimen
 Neosphere
Adding Pertuzumab to trastuzumab and NACT

R
TH q 3w x 4 THP q 3w x 4 HP q 3w x 4 TP q 3w x 4
(n = 107) (n = 107) (n = 107) (n = 96)

Surgery Surgery Surgery Surgery

H q 3w x 13 H q 3w x 13 H q 3w x 13 H q 3w x 17
+ + + +
FEC q 3w x 3 FEC q 3w x 3 T q3w x 4 FEC q 3w x 3

FEC q 3w x 3
T = Docetaxel, H = Trastuzumab, P = Pertuzumab
F = 5-fluorouracil, E = Epirubicin, C = Cyclophosphamide
Gianni L et al. Proc SABCS 2010;Abstract S3-2.
 NEOSPHERE results

These findings led the FDA to grant accelerated

approval of pertuzumab in the neoadjuvant
treatment of HER2+ breast cancer. Ann Surg Oncol. Author manuscript; available in PMC 2015 June 29.
NeoSphere & TRYPHAENA: Dual HER2 targeting with pertuzumab and
trastuzumab added to neoadjuvant chemotherapy further increased pCR rates

NeoSphere1* TRYPHAENA2‡
60 100
90
50
tpCR  95% CI (%)

80

tpCR, %  95% CI
40 70
60
30 39.3
50 63.6
40 56.2 54.7
20 30
10 21.5 20
17.7
11.2
10
0 0
HT PHT PH PT FEC + PH x3 FEC x3 TCH+P x6
 PHT x3  PHT x3
tpCR† tpCR†
* NeoSphere: FEC was given following surgery;
† tpCR ypT0/is yp N0;
‡ TRYPHAENA was a safety study and tpCR was a secondary endpoint.

FEC, 5-fluorouracil, epirubicin, cyclophosphamide; HT, trastuzumab + docetaxel; PHT, pertuzumab–trastuzumab1.+Gianni

docetaxel;
L, et al. Lancet Oncol 2012; 13:25–32;
PH, pertuzumab-trastuzumab; PT, pertuzumab + docetaxel; tpCR, total pathological complete response.2. Schneeweiss A, et al. Ann Oncol 2013; 24:2278–2284.
 Comparative Effectiveness of Neoadjuvant Therapy for
HER2–Positive Breast Cancer: A Network Meta-Analysis

• 10 eligible trials, 2247 patients

• Chemotherapy +\- Anti-HER-2 agents (Trastuzumab, Lapatinib, and
Pertuzumab).
• Results : combining two anti-HER-2 agents with chemotherapy is the
most effective treatment modality in the neoadjuvant setting for HER-2
positive breast cancer.

J Natl Cancer Inst (2014).

PCR translated to improved PFS, risk of relapse remains

NeoSphere: At 5-year analysis, 14% of patients had relapsed

or died
100 100
90 90 86
80 80 8
%1
PHT HT %
70 70
PFS (%)

PFS (%)
60 60
50 86%
50
Overall No tpCR tpCR 5-year PFS with
40 40
population (n = 323) (n = 94) PHT, but a
30 proportion of
5-year PFS, % 76 (71– 85 (76– 30
20 (95% CI) 81) 91) patients still
20 relapse
10 Stratified HR = 0.54 (95% CI: 0.29, 1.00)
10
0
0 12 24 36 48 60 0
Time 0 12 24 36 48 60
(months) Time (months)
PFS was substantially better in patients
achieving a pCR
H, trastuzumab; P, pertuzumab; pCR, pathologic complete response;
PFS, progression-free survival; T, docetaxel; tpCR, total pathologic complete response. Gianni L, et al. Lancet Oncol 2016; 6:791–800. 28
 HER2-positive early breast cancer patients with residual invasive disease following
neoadjuvant chemotherapy combined with HER2-targeted therapy have an increased
risk of recurrence and death

 KATHERINE investigated whether substituting adjuvant T-DM1 for trastuzumab would

improve outcomes for patients with residual invasive cancer following neoadjuvant
therapy
 KATHERINE investigated whether substituting adjuvant T-DM1 for trastuzumab would improve
outcomes for patients with residual invasive cancer following neoadjuvant therapy
KATHERINE Study Design

 cT1-4/N0-3/M0 at presentation (cT1a-b/N0 excluded) T-DM1

 Centrally confirmed HER2-positive breast cancer R 3.6 mg/kg IV Q3W
 Neoadjuvant therapy must have consisted of 1:1 14 cycles
– Minimum of 6 cycles of chemotherapy
• Minimum of 9 weeks of taxane N=1486 Trastuzumab
• Anthracyclines and alkylating agents allowed 6 mg/kg IV Q3W
• All chemotherapy prior to surgery 14 cycles
– Minimum of 9 weeks of trastuzumab
• Second HER2-targeted agent allowed Radiation and endocrine
therapy per protocol and
local guidelines
 Residual invasive tumor in breast or axillary nodes
 Randomization within 12 weeks of surgery

This presentation is the intellectual property of Charles E. Geyer Jr. Contact him at cegeyer@vcu.edu for permission to reprint and/or distribute.
 Adjuvant T-DM1
demonstrated both a
statistically significant
and clinically
meaningful
improvement in IDFS
compared with 100
Invasive Disease-Free Survival
trastuzumab

Invasive Disease-Free Survival Rate (%)

– Unstratified
HR=0.50; 95% CI 80
0.39–0.64; TDM-1 will
P<0.0001
now be the
– 3-year IDFS rate Trastuzumab
improved from
60 new
T-DM1
77.0% to 88.3% standard
(difference=11.3% Trastuzumab T-DM1 adjuvant
) (n=743) (n=743)
40 therapy for
IDFS Events, no. (%) 165 (22.2) 91 (12.2) patients
 Benefit of T-DM1 was Unstratified HR=0.50 (95% CI, 0.39–0.64)
consistent across all
with non-
20
key subgroups P<0.0001 pCR after
including HR status, 3-year IDFS 77.0% 88.3% neoadjuva
extent of residual nt anti
invasive disease, and 0
single or dual anti 0 6 12 18 24 30 36 42 48 54 60 HER2
HER2 Rx Time (months) therapy
No. at Risk
Trastuzumab 743 676 635 594 555 501 342 220 119 38 4
T-DM1 743 707 681 658 633 561 409 255 142 44 4

This presentation is the intellectual property of Charles E. Geyer Jr. Contact him at cegeyer@vcu.edu for permission to reprint and/or distribute.
 Safety Overview

Trastuzumab T-DM1
n=720 n=740
Number of patients with at least one , n (%)
Grade ≥3 AEs 111 (15.4) 190 (25.7)
Serious AEs 58 (8.1) 94 (12.7)
nd will now be the new standard for patients with non-
AE leading
pCR. to treatment discontinuation 15 (2.1) 133 (18.0)
AE with fatal outcome^ 0 1 (0.1)

^Fatal AE was intracranial hemorrhage diagnosed after a fall with platelet count of 55,000.

This presentation is the intellectual property of Charles E. Geyer Jr. Contact him at cegeyer@vcu.edu for permission to reprint and/or distribute.
Triple Negative Breast Cancer
 Importance of PCR in TNBC

Neoadjuvant
Chemotherapy for TNBC
• pCR (ypT0/is N0) rate:
34% (meta-analysis)
poorest
prognosis with
no pCR in
TNBC

Cortazar et al SABCS 2012

San Antonio Breast Cancer Symposium – Cancer Therapy and Research Center at UT Health Science Center December 10-14, 2013
 Chemotherapy in patients with TNBC
Do we need platinum?
• Anthracycline and taxane-based
chemotherapy is the SOC for early TNBC.
Generally if no contraindications anthracycline gBRCA status has been
shown not to be
should be given in eTNBC regimen either associated with higher
neoadjuvant or adjuvant PCR, DFS or OS with
the use of carboplatin
• Cisplatin or carboplatin added into standard compared to non gBRCA
regimens of NEOADJUVANT THERAPY have
shown an absolute improvement in
pathological complete pathological response
rates of about 15% BUT the effect on long-
term disease-free survival and overall survival
is not clear at present.
• Use of platinum in the adjuvant setting is
NACT options for TNBC with Carboplatin

3 large platinum based trials

• Better pCR rate with addition of
platinum- Carboplatin
• very high toxicity
only 60% completed chemo in
GeparSixto due to G3/4
myelosupression

Conclusion:
-higher toxicity
-Uncertainty benefit of platinum

Antracycline+ taxane is still

preferred choice
 Early breast cancer patients of TNBC subtype with residual invasive disease following neoadjuvant chemotherapy
have an increased risk of recurrence and death

Post Operative Chemotherapy in Patients with Residual

Disease after Neoadjuvant Therapy:
CREATE-X Trial

Capecitabine

Stage I-III
HER2 neg Neoadjuvant Surgery No pCR
Chemotherapy
N=910

Observation

Masuda N, et al. N Engl J Med 2017

 CREATE-X: Results

ADJUVANT CAPECITABINE given after standard neoadjuvant chemotherapy

and surgery significantly improve disease-free or overall survival especially in
patients with triple-negative breast cancer
the use of adjuvant platinum agents in unselected patients with TNBC non
beneficial and capecitabine remains the standard therapy.
 CALGB 40603: Addition of Carboplatin to Neoadjuvant
Chemotherapy in Triple Negative Breast Cancer

Weekly Taxol x 12 ddAC x 4

Weekly Taxol x 12
Stage II-III Bevacizumab ddAC x 4
Triple
Negative Weekly Taxol x 12
dd AC x 4
Breast Cancer Carboplatin
Weekly Taxol x 12
Carboplatin ddAC x 4
Bevacizumab
 San Antonio Breast Cancer Symposium – Cancer Therapy and Research Center at UT Health Science Center December 10-14, 2013

CALGB 40603: pCR Breast/Axilla (ypT0/is N0)

41% (35-48%) 54% (48-61%) 44% (38-51%) 52% (45-58%)

N=212 N=221 N=218 N=215

Odds ratio: 1.71 p = 0.0029 Odds ratio: 1.36 p = 0.0570
This presentation is the intellectual property of William Sikov, MD. Contact at wsikov@lifespan.org for permission to reprint or distribute.

More toxic : Difficult to give weekly paclitaxel without growth factors

 Immune Checkpoints

Anti PD-1-PD-L1

Active immunotherapy
using immune
checkpoint blockade
(ICB) represents a novel
therapeutic approach for
a variety of cancers, with
promising activity. ICB
uses mAbs targeting
inhibitory immune
checkpoints and has
demonstrated impressive
results in a variety of
solid tumours and
haematologic
PD-1 is an immune checkpoint receptor expressed malignancies.
by tumor infiltrating lymphocytes, limiting the
function of activated T cells
 PD-1 -immune checkpoint
Immune Escape by receptor expressed by tumor
infiltrating lymphocytes, or
Tumours is an PDL-1 expressed by tumour
established hallmark of interfere with tumour killing
cancer by acvtivated T cells

TNBC – most Active immunotherapy

immunogenic subtype with anti PD-1 or anti PDL1
Importance of PD-
with highest rate of PDL- 1/PD-L1 blockade (checkpoint blockade)
1 exp and Tumour represents a therapeutic
infiltrating lymphocytes approach targeting
inhibitory immune
checkpoints allowing the
activated T cells to kill
cancer cells
NIH. News Headlines: https://ccr.cancer.gov/news/article/investigators-lead-first-human-trials-of-new-immunotherapy-drug
(accessed August 2017)
 Phase III RDB Study to Evaluate Pembrolizumab plus CT vs
Placebo plus CT as Neoadjuvant Therapy and Pembrolizumab vs
Placebo as Adjuvant Therapy for TNBC
 KEYNOTE 522 Results
pCR response was significantly higher
among those who received
Pembrolizumab had produced a
pembrolizumab plus neoadjuvant statistically significant EFS
chemotherapy benefit compared with CT alone

https://www.nejm.org/doi/full/10.1056/NEJMoa1910549
Other immunotherapy studies awaited

Solinas C, et al. ESMO Open 2017;

 KN 522 results
• Addition of the anti-PD-1 antibody pembrolizumab to neoadjuvant paclitaxel and carboplatin followed
by doxorubicin–cyclophosphamide increased the pathological complete response rate by up to 64%.
• The effect was independent of PD-L1 status and mainly seen in node-positive breast cancer.
• Very similar results could be observed with atezolizumab being added to nab- paclitaxel followed by
doxorubicin–cyclophosphamide every 2 weeks in the Impassion 031 study.
• This combination has changed the primary therapy in high-risk early TNBC.
• Patients continued taking the checkpoint inhibitor after surgery for up to 1 year.
 Summary of 19

Recommendations
Clinical Question 4

• What neoadjuvant treatment is recommended for patients with HR-positive/HER2-

negative breast cancer?

Recommendation 4.1
Informal consensus
• Neoadjuvant chemotherapy can be used instead of adjuvant
chemotherapy in any patient with HR-positive, HER2-negative Evidence Quality
Strength of
Recommendati
breast cancer in whom the chemotherapy decision can be made on
without surgical pathology data and/or tumor specific genomic Low Moderate
testing.

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 Summary of 20

Recommendations
Recommendation 4.2 Evidence-based
benefits outweigh harms

• For postmenopausal patients with HR-positive, HER2-negative Evidence Quality

Strength of
Recommendati
disease, neoadjuvant endocrine therapy with an aromatase on

inhibitor may be offered to increase locoregional treatment Intermediate Moderate

options. If there is no intent for surgery, endocrine therapy may be
used for disease control.

Recommendation 4.3 Evidence-based

benefits outweigh harms

• For premenopausal patients with HR-positive, HER2-negative Evidence Quality

Strength of
Recommendati
early-stage disease, neoadjuvant endocrine therapy should not be on

routinely offered outside of a clinical trial. Intermediate Moderate

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For licensing opportunities, contact licensing@asco.org
 To whom is chemotherapy indicated ?

St Gallen consensus, systemic therapy for early breast cancer Nadia Harbeck, Michael Gnant, Lancet 2017; 389: 1134–50
Summary : Treatment Algorithm

www.thelancet.com Vol 397 May 8, 2021

Summary 2: Treatment Algotrithm

www.thelancet.com Vol 397 May 8, 2021