BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE...
Transcript of BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE...
![Page 1: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/1.jpg)
BREAST CANCER: ENDOCRINE THERAPY
Minetta C. Liu, MD Lombardi Comprehensive Cancer Center
Georgetown University Hospital
![Page 2: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/2.jpg)
General Principles of Therapy
• chemotherapy benefits everyone
• endocrine therapy benefits only those with hormone receptor positive disease
![Page 3: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/3.jpg)
ENDOCRINE THERAPY: GENERAL PRINCIPLES
![Page 4: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/4.jpg)
Overview
• The response to endocrine therapy correlates with hormone receptor status.
![Page 5: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/5.jpg)
Overview • Estrogen receptor positivity varies
according to menopausal status.
0 10 20 30 40 50 60 70
ER+/PR+ ER+/PR- ER-/PR+ ER-/PR-
Premenopausal Postmenopausal
Hormone Receptor Status
% o
f Pa
tien
ts
(Beck WW. Obstetrics and Gynecology. 1989.)
![Page 6: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/6.jpg)
Overview • The choice of a particular endocrine
agent is dictated by the primary site of estrogen production.
Corticosteroids
HYPOTHALAMUS
PITUITARY GLAND
Prolactin OVARIES
ACTH
ADRENAL GLAND
Androgens
Growth Hormone Progesterone
PERIPHERAL TISSUES
Estrogens
Estrogens Progesterone
FSH, LH
![Page 7: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/7.jpg)
DRUG OVERVIEWS
![Page 8: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/8.jpg)
Approach to Therapy
• The goal is to minimize interactions between estrogen and its receptor. – reduce the synthesis of estrogen
– interfere with estrogen activity at
the level of the tumor cell
![Page 9: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/9.jpg)
(Clarke et al. Oncogene 2003. 22:7316.)
ER ER
RNA induction RNA inhibition
ERE ERE
Endocrine Therapy: Mechanisms
![Page 10: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/10.jpg)
Endocrine Therapy: History
1900 1925 1950 1975
oophorectomy
ovarian ablation by irradiation
adrenalectomy vs.
hypophysectomy
FDA approves
tamoxifen
high-dose estrogens and
androgens
2000
FDA approves
anastrozole
![Page 11: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/11.jpg)
• sex steroids • estrogen receptor modulators • aromatase inhibitors • pure anti-estrogens • LHRH agonists
Classes of Hormonal Agents
![Page 12: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/12.jpg)
Sex Steroids
• megestrol acetate (Megace)
• fluoxymesterone (Halotestin)
• estrogen
![Page 13: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/13.jpg)
Sex Steroids: Megestrol Acetate
• potential toxicities: – vasomotor instability – weight gain and/or fluid retention – gastrointestinal disturbance – thromboembolic phenomena – hypertension, cardiomyopathy – hyperglycemia, adrenal suppression
![Page 14: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/14.jpg)
Sex Steroids: Fluoxymesterone
• potential toxicities: – acne – facial hair growth – weight gain and/or fluid retention – change in libido – cardiomyopathy – polycythemia
![Page 15: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/15.jpg)
• sex steroids • estrogen receptor modulators • aromatase inhibitors • pure anti-estrogens • LHRH agonists
Classes of Hormonal Agents
![Page 16: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/16.jpg)
• tamoxifen (Nolvadex)
• toremifene (Farnesdon)
• raloxifene (Evista)
Estrogen Receptor Modulators
![Page 17: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/17.jpg)
Estrogen Receptor Modulators: Tamoxifen
• potential toxicities: – vasomotor instability – vaginal discharge, atrophic vaginitis – weight gain – thromboembolic phenomena – liver function abnormalities – uterine hyperplasia or cancer – early cataract development
![Page 18: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/18.jpg)
Estrogen Receptor Modulators: Tamoxifen
• other potential benefits (postmenopausal women): – protection against osteoporosis – improvement in the lipid profile
![Page 19: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/19.jpg)
• sex steroids • estrogen receptor modulators • aromatase inhibitors • pure anti-estrogens • LHRH agonists
Classes of Hormonal Agents
![Page 20: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/20.jpg)
Aromatase Inhibitors
Nonsteroidal Inhibitors • anastrozole (Arimidex)
• letrozole (Femara)
Steroidal Inactivators • exemestane (Aromasin)
![Page 21: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/21.jpg)
Aromatase Inhibitors
• potential toxicities: – vasomotor instability – asthenia – musculoskeletal pain – gastrointestinal upset – vaginal discharge, atrophic vaginitis – accelerated bone density loss
![Page 22: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/22.jpg)
• sex steroids • estrogen receptor modulators • aromatase inhibitors • pure anti-estrogens • LHRH agonists
Classes of Hormonal Agents
![Page 23: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/23.jpg)
Pure Anti-Estrogens
• fulvestrant (Faslodex)
![Page 24: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/24.jpg)
Pure Anti-Estrogens: Fulvestrant
• potential toxicities: – vasomotor instability – peripheral edema – musculoskeletal pain – gastrointestinal upset – pain at the injection site – thromboembolic phenomena – bone marrow suppression
![Page 25: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/25.jpg)
• sex steroids • estrogen receptor modulators • aromatase inhibitors • pure anti-estrogens • LHRH agonists
Classes of Hormonal Agents
![Page 26: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/26.jpg)
LHRH Agonists
• goserelin (Zoladex) • leuprolide (Lupron)
![Page 27: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/27.jpg)
LHRH Agonists
• potential toxicities: – accelerated bone density loss – vasomotor instability – atrophic vaginitis – emotional lability – arthralgias
![Page 28: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/28.jpg)
COMPARISON OF TOXICITIES
![Page 29: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/29.jpg)
SERM’s vs. Progestins
tamoxifen raloxifene megestrol
nausea X X X
weight gain X X XXXXX
hot flashes XX X X
thrombosis XX XX XXXX
altered mood X X X
edema X X XXXX
vaginal discharge XX XX XXX
arthralgias X X XX
uterine changes X none none
![Page 30: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/30.jpg)
Tamoxifen vs. AI’s
tamoxifen anastrozole letrozole exemestane
nausea X XX X X
weight gain X X X X
hot flashes XX XX XX X
thrombosis XX X none none
altered mood X X X none
edema X X X none
vaginal discharge XX X X none
arthralgias X XXX XXX XX
uterine changes X none none none
![Page 31: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/31.jpg)
Tamoxifen vs. Other
tamoxifen fulvestrant LHRH agonists
nausea X XX X
weight gain X X none
hot flashes XX XX XXXX
thrombosis XX X none
altered mood X X X
edema X X none
vaginal discharge XX X none
arthralgias X X none
uterine changes X none none
![Page 32: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/32.jpg)
INDICATIONS
![Page 33: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/33.jpg)
Adjuvant Therapy for Early Stage Breast Cancer:
All Patients
![Page 34: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/34.jpg)
Tamoxifen: The EBCTCG Meta-Analysis
• 55 trials with 37,000 women
• stage I-II breast cancer
• benefits in ER+ or unknown disease only
![Page 35: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/35.jpg)
(EBCTCG. Lancet 1998. 351:1451.)
Tamoxifen vs. Not: The EBCTCG Meta-Analysis
1 year 2 years 5 years
proportional reduction in risk of recurrence 21% 28% 50%
proportional reduction in mortality 14% 18% 28%
![Page 36: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/36.jpg)
(EBCTCG. Lancet 2005. 365:1687.)
Tamoxifen: EBCTCG Analysis
![Page 37: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/37.jpg)
Tamoxifen: Beyond 5 Years
• Do the beneficial effects persist beyond the first five years of treatment?
• Is >5 years of tamoxifen better?
![Page 38: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/38.jpg)
Tamoxifen: NSABP B-14
HR positive postmenopausal
tamoxifen x 5 years
tamoxifen x 5 years
N = 1172
placebo x 5 years
(second randomization)
![Page 39: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/39.jpg)
(Fisher et al. J Natl Cancer Inst 2001. 93:684.)
Tamoxifen: NSABP B-14
10 year course 5 year course p
7 year - DFS 78% 82% 0.03
7 year - OS 91% 94% 0.07
![Page 40: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/40.jpg)
Adjuvant Therapy for Early Stage Breast Cancer:
Postmenopausal Patients
![Page 41: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/41.jpg)
• instead of tamoxifen – anastrozole – letrozole
• in sequence with tamoxifen
– letrozole – exemestane – anastrozole
New Standards?
![Page 42: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/42.jpg)
New Endocrine Strategies
tamoxifen x 2-3 years
initial therapy
sequential therapy
tamoxifen aromatase inhibitor
tamoxifen aromatase inhibitor initial vs. sequential therapy
ATAC, BIG 1-98
ABCSG 8, ARNO 95, ITA, IES
BIG 1-98
aromatase inhibitor TEAM
*
*
*
* tamoxifen aromatase inhibitor
tamoxifen aromatase inhibitor tamoxifen
* aromatase inhibitor tamoxifen
aromatase inhibitor
initial vs. sequential therapy
![Page 43: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/43.jpg)
New Endocrine Strategies
MA 17, ABCSG-6A, NSABP B-33
aromatase inhibitor
placebo tamoxifen x 5 years
* extended sequential therapy
![Page 44: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/44.jpg)
New Endocrine Strategies
absolute DFS reductions at longest follow-up
initial 5 year sequential
extended sequential
3-5% 3-5% 6%
![Page 45: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/45.jpg)
• decreased risk of contralateral disease
• no negative effects on the endometrium
• minimal risk of thromboembolic events
Additional Benefits with Aromatase Inhibitors
![Page 46: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/46.jpg)
• accelerated bone mineral density loss
• arthralgias and/or myalgias
• alterations in the lipid profile
• increased risk of cardiovascular disease
Additional Risks with Aromatase Inhibitors
![Page 47: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/47.jpg)
Adjuvant Therapy for Early Stage Breast Cancer:
Premenopausal Patients
![Page 48: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/48.jpg)
New Standards?
• ovarian functional suppression . . .
• instead of chemotherapy • instead of tamoxifen • with tamoxifen • with an aromatase inhibitor
![Page 49: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/49.jpg)
SOFT
definitive surgery
definitive surgery then
chemotherapy
tamoxifen x 5 years
OFS and tamoxifen x 5 years
OFS and exemestane x 5 years
- OR-
![Page 50: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/50.jpg)
PERCHE
definitive surgery
chemotherapy + OFS + tamoxifen or exemestane
OFS + tamoxifen or exemestane
![Page 51: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/51.jpg)
TEXT
definitive surgery
OFS + tamoxifen
OFS + exemestane
![Page 52: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/52.jpg)
Metastatic Breast Cancer: All Patients
![Page 53: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/53.jpg)
General Principles
• expected responders: 50-60%
• duration of response: 8-14 months
![Page 54: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/54.jpg)
• hormone receptor positive
• long disease free interval *
• bone/soft tissue disease
• sensitive to endocrine therapy
• hormone receptor negative
• short disease free interval *
• extensive visceral disease
• refractory to endocrine therapy
Endocrine therapy Chemotherapy
(* defined in relation to a two year interval from initial diagnosis)
Guiding Principles
![Page 55: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/55.jpg)
Tamoxifen: Advanced Disease
postmenopausal premenopausal
objective response rates 15-53% 20-45%
duration of response 20 months ≤36 months
![Page 56: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/56.jpg)
Metastatic Breast Cancer: Postmenopausal Patients
![Page 57: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/57.jpg)
Aromatase Inhibitors
• anastrozole – vs. megestrol: improved survival – vs. tamoxifen: longer time to progression
• letrozole
– vs. megestrol: no difference – vs. tamoxifen: longer time to progression – vs. anastrozole: no difference
![Page 58: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/58.jpg)
Aromatase Inhibitors
• exemestane – vs. megestrol: longer time to progression – vs. tamoxifen: no difference
![Page 59: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/59.jpg)
Pure Antiestrogens
• fulvestrant
– vs. anastrozole: no difference – vs. exemestane: no difference
![Page 60: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/60.jpg)
Treatment Algorithm
tamoxifen nonsteroidal aromatase inhibitor
pure anti-estrogen steroidal aromatase inhibitor
megestrol acetate androgen or aminoglutethimide
![Page 61: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/61.jpg)
Metastatic Breast Cancer: Premenopausal Patients
![Page 62: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/62.jpg)
Ovarian Functional Suppression
• Small randomized trials suggest that
the combination of ovarian functional suppression and tamoxifen may be superior to tamoxifen alone.
![Page 63: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/63.jpg)
Treatment Algorithm
tamoxifen or LHRH Agonist LHRH Agonist or Tamoxifen
oophorectomy nonsteroidal aromatase inhibitor
pure anti-estrogen steroidal aromatase inhibitor
megestrol acetate androgen or aminoglutethimide
![Page 64: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/64.jpg)
TAKE HOME POINTS
![Page 65: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/65.jpg)
• Tamoxifen is effective for patients with hormone receptor positive breast cancer, irrespective of their menopausal status.
![Page 66: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/66.jpg)
• The nonsteroidal aromatase inhibitors have demonstrated equivalence or superiority to tamoxifen in the management of postmenopausal women.
![Page 67: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/67.jpg)
• Ovarian suppression (or ablation), alone or in combination with tamoxifen, may be equivalent or superior to chemotherapy in the treatment of premenopausal women.
![Page 68: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/68.jpg)
• We have a great deal more to learn with respect to the biology of breast cancer . . .
![Page 69: BREAST CANCER: ENDOCRINE THERAPY - lbbc.org Teleconference.Liu_.02 08 12.pdfBREAST CANCER: ENDOCRINE THERAPY Minetta C. Liu, MD . Lombardi Comprehensive Cancer Center . Georgetown](https://reader034.fdocuments.net/reader034/viewer/2022042301/5ecbac53176b9b18666185c2/html5/thumbnails/69.jpg)
THANK YOU