1) Hormonal therapy targets estrogen receptor positive breast cancers, which comprise around 70% of cases. It works by blocking the effects of estrogen through various mechanisms. 2) Available hormonal therapies include selective estrogen receptor modulators (SERMs) like tamoxifen, aromatase inhibitors, LHRH analogues, and ovarian ablation through surgery or radiation. 3) In the adjuvant setting, 5 years of tamoxifen reduces recurrence and mortality rates in both pre- and postmenopausal women. Longer durations up to 10 years provide further benefits in high risk patients. Aromatase inhibitors are now preferred over tamoxifen for initial therapy in postmenopausal women.

1. HORMONAL THERAPY FOR
BREAST CANCER
Parag Roy
Lok Nayak Hospital

2. INTRODUCTION
◦ Around 60-70% patients diagnosed to have breast cancer are Estrogen receptor-positive (65%
of these are also positive for Progesterone receptors)
◦ Patients with Estrogen receptor-Positive (ER+) tumors have a better survival than tumors with
no Estrogen receptors (ER-)
◦ Five-year survival about 10 percent better for women with ER+ than for those with ER- tumors
◦ Patients with ER + tumors are candidates for hormonal therapy

3. TIMELINE OF DEVELOPMENT OF AGENTS IN
BREAST CANCER

4. MOLECULAR BASIS
◦ Overexpression of Estrogen receptors is seen in a large number of breast cancer patients (~70%)
◦ Estrogen :
◦ Steroid hormone
◦ Profound proliferative effect on normal human mammary epithelium through its activation of ER-alpha, a
classic nuclear hormone receptor
◦ Exerts its actions through both genomical and nongenomical mechanisms

5. Classical genomic mechanism:
(1) Estrogen binds to an intracellular
Estrogen receptor (ER)
(2) ER dimerizes with another ER
(3) ER complex translocates to the nucleus
and then binds to the Estrogen
response element (ERE) leading to
transcription
Non Classical genomic mechanism:
(1) Estrogen binds to a membrane bound
ER
(2) Second messenger systems are
activated
(3) molecules from second messenger
systems bind to DNA regulatory
regions such as cAMP response
element (CRE) and serum response
element (SRE) regions to activate
transcription

6. Non Genomic Mechanism :
- Believed to result from the hormone-
dependent activation of membrane-bound
and/or cytosolic ERs.
- These nonnuclear ER actions result in very
rapid phosphorylation and activation of
important growth regulatory kinases
including
- EGFRs
- IGF-1R
- c-Src
- Shc
- p85 regulatory subunit of PI3-K

7. HORMONAL THERAPY
Hormonal
therapy
Surgical
(ablation)
Medical
SERM
Aromatase
inhibitors
LHRH
analogues
(supression)
Anti estrogens Progestins
Radiotherapy
(ablation)

8. SITE OF ACTION OF HORMONAL DRUGS

9. HORMONE RECEPTOR STATUS AND
PROBABILITY OF RESPONSE TO THERAPY
Estrogen Receptor
Status
Progesterone
Receptor Status
Response Probability
Positive Positive High (50-70%)
Positive Negative Intermediate (33%)
Negative Positive Intermediate (33%)
Negative Negative Low (Less than 10%)
◦ At 10 yrs:
The recurrence rates were reduced by 14% and 11% in node –ve and +ve
patients respectively.
Similarly, mortality reduced by 14.8% and 12% respectively.

10. AGENTS USED IN HORMONAL THERAPY
◦ Selective Estrogen Receptor Modulators (SERM)
◦ Tamoxifen
◦ Raloxifen
◦ Torimefene
◦ Anti Estrogens
◦ Fulvestrant
◦ Aromatase Inhibitors
◦ Letrozole
◦ Anastrazole
◦ Exemestane
LHRH Agonists
Leuprolide
Goserlin
Progestins
Megestrol acetate
Medroxyprogesterone acetate
Gland ablation
Ovary
Pituitary
Adrenals

11. SELECTIVE ESTROGEN RECEPTOR
MODULATORS (SERMs)
◦ TAMOXIFEN
◦ 1st hormonal drug approved by the FDA for usage in Breast Cancer
◦ Chemically : Triphenylethylene
◦ Mechanism of action : Competitive binding to the estrogen receptor resulting
in reduction of transcription of estrogen regulated genes
◦ Blocks the cell cycle in G1 phase
◦ Cytostatic drug

12. ANCILLARY BENEFITS OF TAMOXIFEN
◦ Cardiovascular:
◦ Fewer non cancer related deaths due to cardiovascular events.
◦ Fewer hospitalizations for cardiac events
◦ Serum LDL / cholesterol reduced.
◦ Actual magnitude of benefit still unclear.
◦ Skeletal:
◦ Significant reduction in incidence of fractures of weight bearing bones.
◦ Estrogen agonist action on BMD
◦ Prevention of contralateral breast cancer

13. TOXICITY OF TAMOXIFEN
◦ Menopausal symptoms:
◦ MC in premenopausal
◦ Vaginal dryness and discharge may occur
◦ Depression
◦ Ocular toxicity:
◦ Keratopathy, maculopathy & cataract
◦ Reported with high doses
◦ Thromboembolism:
◦ Complication more common in elderly
patients with metastatic breast cancer and
who are receiving CCT
◦ Carcinogenesis:
◦ Increased risk of endometrial cancers Mostly
low grade & stage I tumors.
◦ Other tumors:
◦ Hepatomas
◦ Clear cell sarcomas of ovary

14. ANTI ESTROGENS
(SELECTIVE
ESTROGEN
RECEPTOR
DOWNREGULATOR)
Fulvestrant
ANTI-
ESTROGENS
Fulvestrant

15. ANTI ESTROGENS
◦ FULVESTRANT
◦ Steroidal antiestrogen.
◦ Considerably higher affinity for Estrogen receptor than tamoxifen
◦ Promotes accelerated ER turnover,
◦ Suppression of ER protein levels,
◦ Inhibition of ER dimerization,
◦ Reduced shuttling of the ER from the cytoplasm to the nucleus
◦ Developed for clinical use as a 250-mg intramuscular monthly depot
injection
◦ Developed to counter the estrogenic effects of Tamoxifen on uterus and the
bone related effects of AIs.

16. AROMATASE
INHIBITORS
Letrozole
Anastrazole
Exemestane

17. AROMATASE INHIBITORS
◦ Work by inhibiting the action of the enzyme aromatase
◦ Peripheral conversion of androgens into estrogens by a process called
aromatization
◦ 2 types available (3rd Generation)
◦ Steroidal Inhibitors : Exemestane
◦ Irreversible Inhibition
◦ Permanent and deactivating bond with the aromatase enzyme
◦ Non steroidal Inhibitors : Letrozole, Anastrazole
◦ Reversible Inhibition
◦ inhibit the synthesis of estrogen via reversible competition for the aromatase enzyme

18. Toxicity
◦ Hot Flushes:
◦ Usually self limiting
◦ HRT/ SSRIs are not recommended
◦ Vaginal Bleeding:
◦ Watch out for an endometrial CA in post menopausal females.
◦ Myalgia / Arthalgia:
◦ Switching to Tamoxifen may be required.
◦ Osteoporosis:
◦ Calcium supplements, Vitamin D and bisphosphonates
◦ HRT / Raloxifen not recommended

19. LHRH
AGONISTS
Leuprolide
Goserelin

20. LHRH ANALOGUES
◦ Analogue that activates the GnRH receptor resulting in increased secretion of FSH and LH
◦ After their initial stimulating action – termed a “flare” effect - eventually causes a paradoxical
and sustained drop in gonadotropin secretion
◦ This second effect is termed “downregulation” and can be observed after about 10 days.
◦ While this phase is reversible upon stopping the medication, it can be maintained when GnRH
agonists use is continued for a long time.

21. PROGESTINS
Megestrol acetate
Medroxyprogesterone
acetate

22. PROGESTINS
◦ Powerful antiandrogenic and antiestrogenic effects
◦ Significantly lowers the expression of the androgen receptor (AR) and the Estrogen receptor (ER)
in the body
◦ The antineoplastic action of progestins on carcinoma of the breast is effected by
◦ modifying the action of other steroid hormones and
◦ by exerting a direct cytotoxic effect on tumor cells

23. HORMONAL THERAPY IN ADJUVANT
SETTING
◦ Tamoxifen is the agent of choice for all pre menopausal patients with Estrogen receptor
positivity
◦ 5 years of adjuvant Tamoxifen reduced the risk of breast cancer recurrence and death at 15
years

24. ◦ Several trials have demonstrated that Tamoxifen adds significantly to the DFS in the adjuvant setting.
◦ Two major trials have also demonstrated a overall survival benefit
Trial Dose Duration DFS OS
NATO 20 2 P < 0.05 P < 0.05
Christie 20 1 P < 0.05 NS
Stockholm 30 2 P < 0.05 NS
CRC 20 2 P < 0.01 NS
Scottish 20 5 P < 0.05 P < 0.05
NAL THERAPY HORMONAL THERAPY IN
ADJUVANT SETTININ ADJUVANT SETTING
HORMONAL THERAPY IN ADJUVANT
SETTING

25. Reduction in Annual Odds*
Recurrence Cancer Deaths Any Deaths
Node negative
0 – 4 yrs 48% 33% 25%
5 + yrs 35% 30% 21%
Node Positive
0 – 4 yrs 41% 40% 29%
5 + yrs 20% 38% 36%
TAMOXIFEN AND NODAL STATUS
Ref : Tamoxifen for early breast cancer: an overview of the randomised
trials Early Breast Cancer Trialists’ Collaborative Group Lancet 1998; 351:
1451–67

26. SOFT TRIAL
N Engl J Med 2015;372:436-46

27. NO DIFFERENCE IN DFS AND FREEDOM FROM BREAST CANCER AT 5 YEARS

28. Exemestane plus Ovarian Suppression had a higher
rate of Freedom From Breast Cancer

29. TAMOXIFEN AND EXEMESTANE
TRIAL(TEXT)
◦ 2 arms
◦ Triptorelin + exemestane
Vs
◦ Triptorelin + tamoxifen
◦ 4690 women were included in the intention to treat population
◦ Median follow up period – 68months
N Engl J Med 2014;371:107-18

30. DFS IS BETTER WITH EXEMESTANE AFTER 5 YEARS
NO DIFFERENCE IN OVERALL SURVIVAL
TREATMENT DISCONTINUE IS MORE WITH EXEMESTANE
(16% Vs 11%)

31. HORMONAL THERAPY IN ADJUVANT
SETTING
◦ Duration of therapy :
◦ Earlier 5 years of Tamoxifen was the recommendation
◦ 2 trials : ATLAS and aTTom have been done to see the advantage of giving Tamoxifen for more than 5
years
◦ Both the trials have confirmed benefits of giving the drug for 10 years in high risk paients
◦ ASCO 2014 Update on adjuvant Hormonal therapy in Breast Cancer recommends the use of Tamoxifen
for 10 years in pre and peri menopausal females with Estrogen receptor positivity

32. ATLAS trail

33. RECURRENCE MORTALITY
Significant reduction in the risk of recurrence and breast cancer
mortality with 10yr of tamoxifen compared with a five-year
treatment course

34. aTTom trial

35. aTTom trial (prelim result)
◦ Between 1991 and 2005, 6,934 women with ER+ (39%), or ER untested (61%) invasive breast
cancer (53% node negative, 31% node positive, 16% node status unspecified)
◦ All completed 4+ years of adjuvant tamoxifen
◦ Randomized between continuing for another 5 years and stopping
◦ Median follow-up of 4.2 years, there were fewer recurrences those allocated to 10yrs than 5yrs
tamoxifen.
◦ Breast cancer mortality was lower among those allocated 10yrs,
◦ Despite a doubling in the risk of endometrial cancer (76 vs 35) with 10yrs tamoxifen, there was
no increase in deaths from endometrial cancer (10 vs 12) or from any other non-breast cancer
cause.
◦ Results are consistent with preliminary findings from the atlas trial

37. HORMONAL THERAPY IN ADJUVANT
SETTING
◦ Aromatase Inhibitors
◦ Have been proven beneficial in Post menopausal setting
◦ No benefit seen in Pre menopausal setting
◦ Presently considered the 1st line hormonal therapy in Post menopausal setting

38. Ref : Perez and Brady’s Principles and Practice of Radiation
Oncology, 6th edition

39. ADJUVANT HORMONAL THERAPY IN
POSTMENOPAUSAL

40. AI produce significantly lower recurrence rates compared with tamoxifen, either as initial
monotherapy or after 2 to 3 years of tamoxifen.

41. MA -17 ATAC BIG IES
Vaginal Complications - 1.7% - 14% - 3.3% - 1.5% Tamoxifen
poorer
Endometrial Cancer NA - 0.6% - 0.4% NA
Thromboembolic events NA - 1.7% - 1.2% - .9%
Cardiac complications 0.5% 0% 0.4% NA AI poorer
Arthalgia /Myalgia 23% 7% NA 6%
Osteoporotic fractures 2.3% 2.2% 1.7& 2%
Hot flushes 6% 5% 4% 2%
TOXICITY OF AROMATASE
INHIBITORS VERSUS TAMOXIFEN

42. HORMONAL THERAPY IN ADJUVANT
SETTING
◦ LHRH Agonists in Early breast Cancer
◦ Several trials have been done which have evaluated the role of LHRH agonists either alone or in
combination with Tamoxifen or chemotherapy in adjuvant setting for Early breast cancer
◦ ZEBRA
◦ ABCSG 05 Trial
◦ GROTA 02 Trial
◦ ZIPP Trial
◦ INT 0101 Trial

43. CHEMOHORMONAL THERAPY
median follow-up of 9.6 years, the addition of tamoxifen to CAF-Z improved TTR and DFS but not
OS. There was no overall advantage for addition of goserelin to CAF

44. TIMING OF ENDOCRINE THERAPY
◦ For women with hormone receptor-positive breast cancer who are not recommended to receive
other adjuvant therapy (eg, chemotherapy and/or radiotherapy), endocrine therapy is usually
initiated four to six weeks after surgery.

45. WITH OR AFTER CHEMOTHERAPY
◦ North American Intergroup trial, 637 postmenopausal women with node-positive,
hormone receptor-positive breast cancer were treated with chemotherapy and
randomly assigned to treatment with tamoxifen initiated during or following
completion of chemotherapy.
◦ At 13 years of follow-up, sequential treatment resulted in:
◦ A trend towards improvement in DFS compared with concurrent treatment (HR 0.84,
95% CI 0.70-1.01)
◦ No improvement in OS (HR 0.90, 95% CI 0.73-1.10)

46. WITH OR FOLLOWING RADIATION
THERAPY
◦ Multiple studies show that the timing of endocrine therapy in relation to RT does not impact
survival
◦ Some older studies suggest that concurrent treatment increases the risks of treatment
complications (including pulmonary and/or breast fibrosis)

47. ◦ Women of childbearing potential — Women who are of childbearing potential should be
advised to use an effective means of contraception while on Tamoxifen treatment because
tamoxifen can induce ovulation.
◦ Following completion of Tamoxifen treatment, a waiting period of two months from drug
discontinuation prior to attempting pregnancy is suggested to ensure that it has been cleared
from the body
◦ Tamoxifen use is contraindicated during pregnancy as it can cause congenital anomaly

48. ENDOCRINE THERAPY IN METASTATIC
BREAST CANCER
◦ Endocrine therapy should be started in all hormone receptor positive females with
metastatic breast cancer.
◦ Hormone therapy may suitable as sole therapy with severe comorbid conditions or very
old age.
◦ AI are standard 2nd line agents after tamoxifen therapy.
◦ Recently evidence has emerged which highlights the superiority of AI in the 1st line setting
too.
◦ In premenopausal females ovarian ablation may be another alternative. It also allows use
of AI in this population.
◦ Selection of the appropriate initial management depends on:
◦ Tempo of the disease (Slower progress, fewer symptoms)
◦ Vital organ involvement ( Bone & Soft tissue)
◦ General condition of the patient (Older age, poorer GC)
◦ Socio economic conditions.

49. OVERALL EFFECT OF ENDOCRINE RX
◦ Bone Mets:
◦ Significant and quick relief of pain
◦ Increased bone calcification and sclerosis
◦ Reduced hypercalcemia and calcium loss.
◦ Better benefit in osteolytic (osteoclastic) leisons.
◦ Skin / soft tissue mets:
◦ Nodular leisons respond better than lymphangitic leisons.
◦ Edema is rarely reduced.
◦ Choroidal metastasis:
◦ Regression and vision recovery may be seen in 10 - 20%
◦ Pleuropulmonary leisons:
◦ Significant number of patients have reduction in size of leisons and effusions.
◦ Systemic effects:
◦ Increased feeling of well being
◦ Reduced incapacitation due to pain
◦ Metastatic leisons that don’t respond:
◦ Hepatic
◦ Cerebral

50. Endocrine Rx in Metastatic CA
◦ Tamoxifen remains the gold standard.
◦ Been in use since 1970s
◦ Began to be used instead of high dose estrogens which were due to
highly favourable side effect profile.
◦ Response rates range from 16% to 56% (Median 30%) – same as
ovarian ablative techniques.
◦ Overall mean TTP for patients with metastatic disease treated with
tamoxifen is about 6 months
◦ Duration of response is between 12 and 18 months

51. AI : 2nd Line therapy
◦ Initially used instead of high dose steroid in tamoxifen resistant
patients.
◦ Showed a small but significant benefit in 5 RCTs in terms of survival and
better side effect profile
◦ However overall the response rates were in the 10% to 20% range
◦ Significant clinical benefit from Aromatase inhibitors often occurs in
the absence of dramatic disease regression.
◦ Therefore now the standard 2nd line endocrine therapy in tamoxifen
resistant metastatic breast cancer.

52. AI : 1st line therapy
◦ 3 major pahse III trials have directly compared tamoxifen against AI.
◦ All have shown an improvement in time to progression (TTP)
◦ The study by the International Letrozole Breast Cancer Group is the
largest in the series.
Trial Drug N RR TTP (mo) Comment
Nabholtz et
al1
Ana 353 21% 11.1* Retrospective
analysis revealed
longer TTP with
Anastrazole after
combining these
two trials3,4
Tmx 17.7% 5.6
TARGET trail2 Ana 668 32.9% 8.2
Tmx 32.6% 8.3
Mouridsen et
al5
Let 907 30% 9.4
Tmx 20% 6.0

53. AI : 1st line therapy
◦ Several trials have shown that the TTP is significantly improved in metastatic
breast cancer when AI are used as 1st line therapy instead of tamoxifen.
◦ The impact on OS not clear however.
◦ In the trail comparing Letrozole to Tamoxifen it was shown that OS improved
in the first 2 yrs.
◦ However no benefit exists at 5yrs.
◦ However due to crossing over a significant impact on OS may have been lost.
◦ Crossing over to Tamoxifen after initial AI therapy may be theoretically unwise
as:
◦ Estrogen deprived cancer cells may be become paradoxically sensitive to tamoxifen.

54. AI : 1st line therapy
◦ Toxicity:
◦ Patients on AI therapy have experienced significantly lesser thromboembolic
phenomenon.
◦ However the incidence of hot flashes is increased.
◦ There have been no trials which showed a benefit of one AI over
another.
◦ One trial comparing Letrozole vs Anastrozole failed to show a
difference in TTP or other parameters.
◦ Because intratumoral Aromatase inhibition is most important so it s
unlikely any particular AI will be more beneficial over the other.

55. Treatment after progression on AI
◦ Progression after 1st line AI therapy is difficult to tackle.
◦ A retrospective analysis has shown that objective response after
tamoxifen therapy is of the order of 10% after AI failure.
◦ Another phase II trial has shown that Exemestane may be associated
with a response rate of 6.6% after Letrozole / Anastrazole therapy.
◦ No endocrine therapy is thus available that can give promising results
after AI failure.

56. Fulvestrant
◦ A potent inhibitor of estrogen-dependent transcription.
◦ In preclinical models, Fulvestrant was found to be effective against
tamoxifen-resistant MCF7 cell xenografts.
◦ In a trial comparing 1st line tamoxifen vs fulvestrant, no advantage
was obtained in TTP or overall response over tamoxifen.
◦ Given easier use of AI / Tamoxifen place in therapy remains
questionable.
Trial N
Response
Rates (%)
Stable
Disease ≥ 24
wk (%)
Time to
Progression
(mo)
Osborne
et al
An
400
17.5 18.6 3.4
Ful 17.5 24.8 5.4
Howell
et al
Ana
451
15.7 45 5.1
Ful 20.7 44.6 5.4

57. Ovarian Ablation
◦ In a 2001 meta analysis by Klijn et al
comparing adjuvant Tamoxifen +
LHRH agonist vs LHRH agonist alone in
advanced breast cancer:
◦ 22% reduction in the hazard of death for
the combined treatment group
◦ 30% reduction in the hazard of
progression/death for the combined
treatment group.
◦ Median duration of response in patients
receiving combined treatment was 602
days, compared with a median of 350
days in those receiving LHRH agonist
alone
Klijn, J. G. M. et al. J Natl Cancer Inst
2000;92:903-911
LHRH
alone
LHRH
+
Tmx
TMX
alone

58. High Dose Estrogens
◦ Considered only in postmenopausal women as ineffective before the menopause
◦ Activation of the FAS cell death receptor  therapeutic response
◦ Estrogen deprivation  upregulation of FAS receptor
◦ Estrogen  FAS ligand expression
◦ Reduction in serum IGF -1 and 2 levels.
◦ Reasonable alternative to chemotherapy in setting of failure to initial hormonal therapy
(old age / poor GC)
◦ Doses:
◦ DES – 5 mg TDS
◦ Ethinyl Estradiaol: 30 mg in 3 – 4 divided doses
◦ Contraindication:
◦ DVT
◦ Cardiac problems
◦ Can produce objective responses in ~ 30 – 40% patients who have received endocrine
therapy.

59. Progestins
◦ Useful in some selected patients who have developed resistance to SERM and
AIs
◦ Megestrol acetate is used (160 mg /d)
◦ C/I include:
◦ Thromboembolic events
◦ Diabetes
◦ Needs evaluation in phase II trials for usefulness as 3rd line agent.
◦ MOA:
◦ ? Aromatase inhibition
◦ ? Estrogen turnover increased (Estrogen deprivation)
◦ ? Separate action through PRs.

60. Other ablative procedures
◦ Adrenalectomy:
◦ Adrenals are source of estrogen in PM female.
◦ In large series ( 1950s – 60s) objective response rates varied from 28% - 59% (Mean
42%)
◦ Duration of benefit varied from 12 – 36 months.
◦ Necessity for life long hormone replacement and high operative mortality 
obsolescence.
◦ Hypophysectomy:
◦ Another ablative procedure associated with response rates ranging from 40% - 50%
◦ Response duration ~ 18 months
◦ Better tolerance than adrenalectomy made this procedure a better choice.

61. Radiation Hypophysectomy
◦ Need to deliver doses in range of 100 Gy – 200 Gy to bring pituitary
ablation.
◦ Investigators in the Berkley university have used proton beam therapy (
50 Gy x 6 # = 300 Gy)
◦ This dose ablated 90% of the pituitary glands with minimal morbidity.
◦ Growth Hormone  Thyroid hormones  Gonadotropin  Estrogen
and Progesterone  Corticosteroid.

62. HORMONAL THERAPY IN
NEO ADJUVANT SETTING
◦ Limited data
◦ Mostly used in patients with locally advanced breast cancer who are deemed unfit for systemic
chemotherapy
◦ Responses are slower than neo adjuvant chemotherapy
◦ Rates of pathological complete response (pCR) are also less than neo adjuvant chemotherapy

63. ◦ IMPACT Trial :
◦ Immediate Pre operative Anastrazole, Tamoxifen or Combined with Tamoxifen Trial
◦ 330 Estrogen receptor positive post menopausal females randomised to 1:1:1
◦ Response rates of 36% to 39%
◦ Only 1% to 3% achieving a clinical complete response
◦ Rates of breast conservation after 3 months of neo adjuvant hormone treatment were highest in the
anastrozole-alone arm
HORMONAL THERAPY IN
NEO ADJUVANT SETTING

64. ◦ PROACT Trial :
◦ Pre operative “Arimidex” compared to Tamoxifen Trial
◦ Objective responses for anastrozole and tamoxifen occurred in 39.5% and 35.4% of patients,
(ultrasound measurements), and 50.0% and 46.2% of patients respectively (caliper measurements).
◦ Anastrozole is an effective and well-tolerated preoperative therapy,producing clinically beneficial tumor
downstaging and reductions in tumor volume
◦ Anastrozole appears to be at least as effective as tamoxifen
HORMONAL THERAPY IN
NEO ADJUVANT SETTING

65. HORMONAL THERAPY IN PREVENTION
OF BREAST CANCER
◦ The BCPT trial (NSABP P1) was designed to evaluate the efficacy of Tamoxifen
given for 5yrs in high risk population
49% reduction in invasive breast cancer
50% reduction in non invasive cancers
ER +ve tumors were much less frequent in women receiving tamoxifen
Incidence of ER –ve tumors remained same
Reduction in rates of occurrence of tumors of all sizes
◦ The FDA has now approved the use of tamoxifen in high risk women to reduce
breast cancer incidence.
◦ STAR trial evaluated role of Raloxifen in prevention of breast cancer

66. CONCLUSIONS
◦ Endocrine therapy is a safe and well tolerated targeted treatment modality in majority of
patients with breast cancer.
◦ In the adjuvant setting primary treatment with Tamoxifen should be considered in all receptor
positive pre menopausal females.
◦ Ovarian ablation may have additive benefits with Tamoxifen in premenopausal females.
◦ Aromatase Inhibitors have a major role to play in hormone positive post menopausal females

67. CONCLUSIONS
◦ There is insufficient data on neo adjuvant hormonal therapy presently
◦ However, it can be considered in hormone positive females who have a poor general condition
or have contraindications for systemic chemotherapy
◦ In the setting of metastatic breast cancer, hormone receptor positivity gives a lot of options to
be utilised in cases of failure on one therapy or progression on one therapy
◦ Hormonal therapies have also been found useful in chemo prevention, however, sufficient data
is lacking for routine usage

68. Thank you !!!