EARLY BREAST CANCER

RENEWED PARADIGM IN PATIENT CARE

M. Yadi Permana
Fatmawati General Hospital
Jakarta

5th JSOF 28 Juni 2019

 ST. GALLEN/VIENNA 2019: A BRIEF SUMMARY OF
THE CONSENSUS DISCUSSION ON THE OPTIMAL
PRIMARY BREAST CANCER TREATMENT
• Genetic Testing and Pathology
• Surgery of Primary Tumor and Management Axilla
• Adjuvant Hormonal therapy
• Adjuvant and Neoadjuvant Chemotherapy
• Radiotherapy
• Conclusion
 GENETIC TESTING
• The majority of the panelists did not support the idea of all women with breast
cancer being offered genetic counselling
• Individualized approach for genetic testing:

conditions YES NO

Patients with (+) family history 100% -

Aged <35 years at diagnosis 95.9% 4.1%

Unselected patients at ages <50 years 37.2% 65.3%

TNBC < 60 years 85.4% 14.6%

TNBC at any age 38.8% 59.2%

 PATHOLOGY

genomic assay for chemotherapy decision making Ideal cut-off for endocrine therapy prescription
In ER+ tumors

32%
31%
38%

mainly
49%

30% 20%

Cases:
ER+ HER2- N0 T3 N0 any T and 1-3 positive nodes ER <10% ER ≥ 10% did not see ideal cut off
 PATHOLOGY

• Tumor-infiltrating lymphocytes (TILs), 66% of the panelists recommend routine characterization

and reporting. Yet, a majority of 90% would not decide upon indication for or de-escalation (79%)
of chemotherapy based on high TILs.

• Only 28% of the panelists stated that they routinely have TILs analysis reported in their own clinics.

• In luminal A-like tumors (ER+ HER2– G1) and low-risk multigene signatures  chemotherapy only
in the infrequent case of ≥4 involved LNs.
 SURGERY OF THE PRIMARY TUMOR

• “No tumor on ink” had finally been firmly established in 2017 as the standard for
unifocal residual breast cancers and breast-conserving procedures
• “No tumor on ink”  Also be used for multifocal residual disease (provided that breast
radiotherapy is planned)
• 73% of the panel declining lobular cancer, and 62% declining for patients with
extensive intraductal component as the basic requirements for breast conserving surgery
(with radiotherapy planned
• Skin-sparing and nipple-sparing techniques were declined for patients with baseline
inflammatory breast cancer, even when a complete clinical response is achieved (83%);
 MANAGEMENT OF AXILLA

• The Panel decline:

- SLNB in specific low-risk or comorbidity situations (such as T1 luminal A, age > 70 years,
comorbidities).
- SLNB omission for any T2 tumor (89%)
• axillary ultrasound should be mandatory in complementing clinical palpation.

30%
in all cases
44%
• Axillary Radiotherapy (Z011 criteria) in aggressive histology (eg. TNBC)

not necessary
26%
 MANAGEMENT OF AXILLA

• The panel extended the strategies for 1-2 positive sentinel nodes (SNs) to be applicable to mastectomy situations:
TNBC
Regional nodal
Irradiation (RNI)
planned
1. example 30% axillary radiotherapy should be
ER (+) given in accordance with the
HER 2 (+)
44% AMAROS approach in such
situations

depends on tumor biology (e.g.,

2. But there was no clear vote on the details ER+ vs. TNBC)
following with axillary lymph node
26% dissection (ALND)

3. In the absence of RNI, ALND must still be done for mastectomy and 1–2 positive SNs (66%).
Z011 & AMAROS COMPARISON
 MANAGEMENT OF AXILLA

• ALND in cN1  PST cNO :

√ X
≥3 negative SNs Only 1 or 2 SNs
were retrieved obtained

When a
micrometastasis
found in 1 SN
 RADIOTHERAPY
RNI

> 4 positive nodes 1-3 positive nodes cN1  PST

Applied in all 56% panelists: 44% panelists: 23%

29%: 17%:
regional nodes Only if the present only when post- Only if risk
RNI should be Not
features are poor (eg PST SLNB has factors are
indicated recommend
TNBC, residual retrieved negative present
RNI
disease after PST SN
 RADIOTHERAPY
• post-mastectomy radiotherapy (PMRT; chest wall and RNI):
conditions YES NO
pT3 N0 56% 44%
N+ 1-3 ER+ or HER2+ 43% 43%
N+1-3 with adverse features (eg TNBC) 85% 8%
pT2 pN0 with bad features 28% 64%
1-2 positive nodes but no axillary dissection 66% 17%

• For patients who have had mastectomy and immediate breast reconstruction, PMRT indications should remain the same as for
those without immediate breast reconstruction.
• For elderly patients with stage 1 ER+ disease, the majority was not prepared to leave out radiotherapy after breast conservation
(58%), but 62% of the panelists willing to forgo radiotherapy in such cases when the age limit was set to 80 years.
 ADJUVANT ENDOCRINE THERAPY FOR
PREMENOPAUSAL PATIENTS

• Indication for ovarian function suppression (OFS):

√ • has prior chemotherapy X

as clinicopathological
indication (68,1%) • patients with moderate
risk without prior
• age ≤ 35 years (84,8%)
chemotherapy (45,8%)
• ≥ 1 LN involved (37,8%) • patients with HER2+
• ≥ 4 LN involved (17,8%) (52,1%)
• has adverse result in
multigene assay (59,6%)

• In a 33-year-old patient (pN+ ER+ PR+ G3, adjuvant chemotherapy planned), would opt for OFS
plus either tamoxifen or an aromatase inhibitor (AI) depending on tolerance. considered 5 years as
the appropriate duration for OFS
ADJUVANT ENDOCRINE THERAPY FOR
POSTMENOPAUSAL PATIENTS
AI for post menopausal patients

95.70% 93.80%

83.00%

68.10%
59.20%

for patients
with
for all higher risk grade ≥3
at stage HER 2+
patients Ki-67

used at some point of as upfront treatment parameter for inclussion of AI

treatment
 DURATION FOR ADJUVANT ENDOCRINE
THERAPY
Stage 1 disease 54,3% stop tamoxifen after 5 years

Pre menopausal
Stage 2 (N+) or stage 3 disease 79,6% continue tamoxifen up to 10 years

72,3% stop tamoxifen after 5 years

Duration Stage 1 disease
78,3% continue AI after 5 years

68,1% continue tamoxifen after 5 years

Post menopausal Stage 2 (N0) disease
59,2% stop AI after 5 years

97,9% continue tamoxifen after 5 years

Stage 2 (N+) disease
81,2% continue AI after 5 years

• overall, 58% stated that extended adjuvant therapy should last for 10 years. with high risk disease
(e.g. ≥ 10 involved LNs), 60,4% decide to continue endocrine therapy beyond 10 years on a case-
by-case basis
 NEODJUVANT ENDOCRINE THERAPY

• 81.2% would opt for neoadjuvant endocrine therapy for post menopausal patient with a luminal
A-like tumor
• duration for neoadjuvant endocrine therapy
41%

59%

until the optimal reduction in tumor size achieved ≥ 6 months

 ADJUVANT & NEOADJUVANT
CHEMOTHERAPY
• Chemotherapy in luminal A breast cancer

indication for chemotherapy neoadjuvant treatment for postmenopausal luminal A subtype

19%
24%

41%

59%

81%
76%

endocrine therapy chemotherapy

2-3 positive LNs 4-9 positive Lns 6 months until optimal response achieved
The results were very similar to the
decision made regarding lobular cancer.
 ADJUVANT & NEOADJUVANT
CHEMOTHERAPY
• Chemotherapy based on TAILORx, PlanB and MINDACT study 41.7% chemotherapy & endocrine theerapy

25% OFS + endocrine therapy

Age <50 years, node negative, RS 21-25 10.4% chemo + OFS + endocrine therapy
16.6% tamoxifen only
TAILORx

57.1% chemotherapy, based on histopatologic

caracteristics
Postmenopausal, RS >26
28.8% routinely chemotherapy
4.1% chemotherapy just for RS >30
trial
PlanB Age >=50, 1-2 positiveLNs, RS 78.7% omitted chemotherapy
<11

Age 78.7% against chemotherapy

MINDACT
Patient with low
MammaPrint result <50

Age >=50, 1-2

positive LNs 80,9% forgoing chemotherapy
 ADJUVANT & NEOADJUVANT
CHEMOTHERAPY
• For ER+ breast cancers, a majority of the panelists (55.4%) choose alkylators and taxanes (i.e., the TC regimen)
over combinations of anthracyclines, alkylators, and taxanes.

• Chemotherapy in TNBC:
93.30%
chemotherapy regimen

17%

52.20%

30.40%

83% 6.70%

stage 1 stage 2 & 3

anthracyclines, alkylators, and taxanes alkylators and taxanes only

 ADJUVANT & NEOADJUVANT
CHEMOTHERAPY
 Platinum-based regimen chemotherapy

• 53.1% didn’t accept the use of platinum-based regimen in neoadjuvant treatment of all TNBC
patients, depending on stage and disease risk due to the consistency of improvement of pCR
throughout the studies.

• 67.3% panelists voted to include platinum in neoadjuvant treatment for BRCA-mutated patients
despite recent evidence suggesting that there was no increase in pCR depending on the BRCA
status.
 ADJUVANT & NEOADJUVANT
CHEMOTHERAPY
Chemotherapy for HER 2+ early breast cancer

• For T1a HER2+ early breast cancer, 42.6% of the panelists supported anti-HER2 therapy, while
55.6% did not. However, 61.7% agreed that the ER status does not affect any of the thresholds
55.6% didn’t support anti HER-2 therapy

T1a 42.6% supportanti-HER 2 therapy

HER 2+
breast 73.5% TH adjuvant treatment (taxane & trastuzumab)
cancer
Stage 1 disease 4.1% THP treatment

Most preffered:
AC/EC followed by taxane in combination with T and
P
Stage 2 (N+) &
stage 3 14.3% docetaxel + carboplatin with T and P

4.1% AC/EC followed by taxane and pertuzumab only

 ADJUVANT & NEOADJUVANT
CHEMOTHERAPY
 HER 2+ neoadjuvant treatment 52.1% didn’t support pertuzumab + trastuzumab

Stage 1 disease 48.9% pertuzumab shouldn’t be added

25.2% recommend additional pertuzumab on ER - disease

Pertuzumab as
neoadjuvant 76.6% pertuzumab should be added in all cases
treatment
Stage 2 (N+) &
stage 3 19.1% peruzumab in addition to trastuzumab only in ER- disease

12 months 89.9% agreed

duration
29.2% agree for stage 1 patients
6 months
64.6% didn’t support prior selection for shorter duration
During the discussion, 6 months
considered an acceptable option for
patients with clinical reason for
discontiunation
 ADJUVANT & NEOADJUVANT
CHEMOTHERAPY
• Measuring residual cancer after neoadjuvant treatment may be specifically highlighted as a potential assessment for patients at
risk and in need of further intensified treatment.

• Chemotherapy for TNBC patients who have:

83.3% add capecitabine to adjuvant treatment
Residual cancer in axillary LNs 6.2 wouldn’t add any treatment
or the breast (>= 1xm residual
cancer and/or LN + 4.2% use CMF as additional adjuvant treatment
neoadjuvant sequential anthracycline
and alkylator chemotherapy followed
by taxanes
51% recommend capecitabine
Residual cancer <1 cm and no
TNBC residual tumors in LNs
patients 38.8% not recommend further chemotherapy
with
neoadjuvant
treatment
neoadjuvant AC/EC Residual cancer in 91.7% preffered TDM1 as adjuvant systemic therapy
followed by TH (w/o P) breast and/or axilla

TCHP or AC/EC residual cancer in tumors

> 1 cm and/ or an axilla, 93.9% recommend TDM1
followed by taxane with
again
H and P
 ADJUVANT BONE-TARGETED THERAPIES
• the 2017 St. Gallen Consensus Conference  adjuvant bisphosphonate as a standard of care for post
menopausal patients regardless of BMD according to Dhesy-Thind et al & EBCTG report

Pre menopausal 53.1% used in patients on ovarian

suprresion with tamoxifen or AI
adjuvant
bisphosphonate
treatment
Post menopausal 83.7% used to improve DFS

• Denosumab 60 mg twice a year should not be used as a substitute for bisphosphonate as suggested by the
ABCSG-18 Trial
 CONCLUSION

Tailoring therapies improving the management of early breast cancer.

In the future genetic testing play important rules for tailoring therapy.
Standard pathological features seem adequate to define clinically useful groups such
as triple-negative, hormone receptornegative and HER2-positive and hormone
receptor-positive\and HER2-positive tumors for which treatment recommendations