Transcript The preoperative endocrine prognostic index PEPI score

THBT neoadjuvant endocrine therapy is to be used
in post-menopausal breast cancer woman
Antonino Grassadonia
Università «G. D’Annunzio» – Chieti-Pescara
Silvana LEO
USS Oncologia Geriatrica
Lecce
Neoadjuvant endocrine therapy in the management of
breast cancer is woefully underutilized by U.S. clinicians
Judy C. Boughey, MB, BChir, Professor and
Research Chair in the Department of
Surgery at the Mayo Clinic, Rochester.
Matthew Ellis, MD, PhD, Director of the Lester and Sue
Smith Breast Cancer and Professor of Medicine and
Cellular and Molecular Biology at Baylor College of
Medicine, Houston
Judy C. Boughey, MB, BChir, Professor and
Research Chair in the Department of Surgery at
the Mayo Clinic, Rochester.
In postmenopausal women with estrogen receptor–rich tumors,
neoadjuvant endocrine therapy is often a better choice than
neoadjuvant chemotherapy, for a number of reasons
greatest benefit in patients with strongly HR positive disease
Low toxicity
Can significantly dowstage the extent of disease
Increase breast conservation rates
Miami BC conference 2016
Matthew Ellis, MD, PhD, Director of the Lester
and Sue Smith Breast Cancer and Professor of
Medicine and Cellular and Molecular Biology at
Baylor College of Medicine, Houston
Low percent of elegible patients :
3.2% (National Cancer data Base 2012)
2.9% (Surgical Oncology annual Cancer Symposium 2016)
Over 50 y, HR+, T2-T4
11% (T4) (Surgical Oncology annual Cancer Symposium 2016)
One-fourth of patients with T3 and T4 tumors treated with neoadjuvant
endocrine therapy were able to have breast-conserving surgery
Response Indicators ?
Neoadjuvant endocrine therapy in the management of
breast cancer is underutilized by Italian clinicians?
Antonino Grassadonia
Università «G. D’Annunzio» – Chieti-Pescara
Neoadjuvant endocrine therapy versus neoadjuvant chemotherapy:
what is the evidence?
The NEOCENT trial which was designed to compare NCT (FEC100) to NET (letrozole) in postmenopausal
women with strongly HR+ primary BC, was unfortunately prema-turely closed because of slow accrual, and it is
therefore unlikely to contribute in clarifying this critically important question
Restricted to elderly or frail
patients who were felt to be
unsuitable for chemotherapy or
ineligible for surgery ?
which is the best choice?
Randomised clinical trials comparing different endocrine agents in the neoadjuvant setting.
study prospectively
These results, suggest that the effectiveness of the three commercially
available AIs are largely equivalent.
Barroso-Sousa R et al.ecancer 2016
What is the optimum duration of neoadjuvant endocrine treatment?
Randomised clinical trials comparing different endocrine agents in the neoadjuvant setting.
is there a theoretical risk that genomic events such deleterious
resistance-inducing mutations would start to arise during the treatment?
Barroso-Sousa R et al.ecancer 2016
BCS was performed in 121 (84 %) of 144 patients
45%
46%
43%
85 % of patients receiving NET for more than 5 months.
The grade G1 is a tumor biological characteristic
strongly associated with longer DFS and OS
Are there any validated biomarkers to predict short (response) and/or
long-term (recurrence/death) outcome?
Ki-67
PEPI score
(preoperative endocrine prognostic index)
Ki-67
a surrogate of response to endocrine therapy ?
Clinical utility of on-treatment Ki67 level measured in NET trials at different time-points.
Surgery
Which the best time point to assess Ki-67?
One potential limitation of the early assessment of Ki-67 is the development of delayed
or acquired resistance
Barroso-Sousa R et al.ecancer 2016
In the United States, we are routinely giving neoadjuvant CHT, but based
on our PEPI model, one-third of pts did not even need CHT since
endocrine therapy alone was sufficient to control their disease long term
PEPI score
The preoperative endocrine prognostic index PEPI score
was developed
Ellis M et al J Natl Cancer 2008,Barroso-Sousa R et al ecancer 2016
The FUTURE?
Ki-67
POETIC TRIAL
PEPI score
the advantage of measuring two-week Ki67 instead of pretreatment
Ki67 is being prospectively investigated in the large (n = 4.000) perioperative endocrine therapy for individualising care window-ofopportunity trial.(to predict response from adjuvant endocrine therapy
ALTERNATE trial
2280 postmenopausal women with clinical stage II or III HR+,
HER-2-negative BC to receive NET with anastrozole, fulvestrant,
(Alliance A011106 )
or the combination of these two drugs for 24 weeks.
Ki-67 is >10%, pts are recommended to
switch to 12 weeks of weekly paclitaxel for the
determination of the pCR in this population.
Ki-67 <10% will continue their assigned regimen
to complete 24 weeks of NET followed by surgery
and PEPI score calculation
The FUTURE?
Ki-67
Study that aims to evaluate the role of Ki-67 as an early predictive
surrogate marker for therapy response under a short induction
treatment
German ADAPT
HR+,HER-2 negative
postmenopausal women will receive a three week induction
with AI, HC evaluation of Ki-67 will be determined by
central pathology and the measurements will be performed
from the diagnostic core biopsy tumour sample and the
repeat core biopsy after induction therapy . Optimal therapy
response is defined as a drop of Ki-67 to or below 10%
the Ki-67 value after the induction therapy, treatment decision will be based on pretreatment
risk assessment (recurrence score (RS) by the OncotypeDx® and nodal status
Non responders (post-therapeutic Ki-67 >10%) and patients initially identified as
high-risk for recurrence (N2-3 or N0-1 and RS ≥ 26) will be randomised to a
chemotherapy protocol optimising dose-dense taxane-based chemotherapy.
Network diagram of studies comparing clinical objective
response (COR) of different neoadjuvant endocrine therapy
(NET) therapies for HR-positive breast cancer.
CONCLUSION: our study proved that letrozole plus everolimus is the most effective treatment
for postmeno- pausal, HR-positive breast cancer in the neoadjuvant setting. In addition, when
patients have hot flushes during the period of NET, NSAIDs, such as celecoxib, are
recommended.
Importantly, one should keep in mind that the decision to
prescribe NET to a given patient is not necessarily an
irreversible one; in case of poor clinical response, the
treatment can be switched to immediate surgery or
chemotherapy.
Antonino Grassadonia
Università «G. D’Annunzio» – Chieti-Pescara
[email protected]