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HORMONE THERAPY IN BREAST CANCER
By Dr. Rajib Bhattacharjee
Sir George Thomas Beatson
“ovaries may be the
exciting cause of
cancer of breast”
Beatson CT. On treatment of inoperable c...
Hormone -
definition
“A hormone is a class of
regulatory biochemical that
is produced in all organisms
by glands, and tran...
Hormone responsive malignancies
Endometrium
Prostate
Breast
Hormone receptor +ve breast cancer
histology-ductal,lobular,mixed,metaplastic (STAGE I-III)
HER2neu +ve
Node +ve node –ve
...
Hormone receptor +ve breast cancer
Histology- Tubular, Mucinous (STAGE I-III)
node +ve node –ve
HT+/- CT <=1cm 1-2.9cm >=3...
Hormone receptor +ve breast cancer
STAGE IV or recurrent disease
No prior HT within 1 yr Prior HT within 1 yr
premeno post...
Adjuvant hormone therapy
pre-menopausal @ diagnosis post-menopausal @ diagnosis
Tamoxifen(5 yrs) / OS / OA AI(5 yrs) AI(2-...
Endocrine therapy
surgical radiotherapy hormonal agents
Oophorectomy Ovarian ablation
Hormone receptor status &
probability of response to therapy
ER status PR status Response probability
Positive Positive hi...
Hormonal agents in breast cancer
Class of drug Individual drug dose Route of
delivery
Frequency of
delivary
SERM Tamoxifen...
SERM
3rd Generation
Lasofexifen
2nd Generation
Raloxifen
1st Generation
Tamoxifen Toremifen
Tamoxifen
Mechanism of action
 Tamoxifen binds competitively to ER Tamox-ER dimer
binds to ER elements nucleus
inhibits t...
Tamoxifen
FDA approved indications
 Prevention of premenopausal breast cancer
 Treatment of DCIS
 Treatment of surgical...
Tamoxifen
Drug interactions --Tamoxifen inhibits hepatic P450 system
metabolism
Warfarin Cyclophosphamide
Antidepressants(...
Tamoxifen
Caution
 Vaginal bleeding, pelvic pain
refer to gynaecologist
 Abnormal liver function
drug accumulation
toxic...
Tumor flare
 Incidence:
4% to 7% with high-dose estrogen
3% to 13% with tamoxifen
 Dramatic  in bone pain, an  in size...
Contra-indications of Tamoxifen
ABSOLUTE
 Retinal macular edema or
degeneration
 H/O benign or malignant liver
tumor sec...
Raloxifen
Estrogen agonist action Estrogen antagonist action
Bone liver breast endometrium
Treat osteoporosis cholesterol ...
Arometase inhibitor
Steroidal AI (type 1) Non steroidal AI(type 2)
MOA Steroidal AI
Binds irreversibly with
active site of...
Anastrazole & Letrozole
Anastrazole
 Bone density measurement needs
to be performed prior to initiation
of treatment & at...
SERD-Fulvestrant
 MOA- High affinity for ER
Downregulates expression of ER
 Indications- metastatic hormone receptor pos...
GnRH Analogues
Goserelin & Leuprolide
 They are used for Medical Ovarian Suppression
 MOA- Desensitisation of pituitary ...
Megestrol acetate
 MOA- Direct anti-estrogenic effect
inhibits LH receptor
inhibits stability, availability & turnover of...
Antiandrogens
Luminal ER-/AR+ Breast cancer
 A molecular subtype of breast cancer which is not sensitive to
antiestrogens...
So many arrows in our repertoire…..which
one to shoot….
Tamoxifen for 5 years
 41% reduction in the annual rate of breast...
Tamoxifen for how long…?
Tamoxifen is recomended for 5 years in our clinical practice
Cause – 1. Carry over effect
2. Risk...
To AI or not to AI… that is the problem…
Timing /
setting
Trial AI No. of pt Hazard ratio
for DFS
Absolute diff
in DFS
Upf...
How to attack.....??
ATAC Trial
ER +ve Breast Cancer in a postmenopausal woman (n=9366)
Arimidex Tamoxifen combination
1mg...
A big trial comparing four arms
BIG 1-98Trial
Post menopausal ER positive breast cancer(n=8010)
LTZ for 5 yrs TAM for 5 yr...
ITA- a sequential trial
ER+ postmenopausal node positive breast ca(n=448)
TAM for 5 yrs TAM for 2-3 yrs
ANZ for 3-2 yrs
me...
Mother of all trials...?
MA.17Trial
Post menopausal, receptor +ve woman, who have completed 4.5 - 6yrs of
Tamoxifen and re...
Upfront vs Sequential or Extended
therapy
ITA & ARNO/ABCSGTrials support the benifits of switching from
Tamoxifen to Anast...
Upfront vs Sequential or Extended
therapy
Punglia et al (JCO 2005; 23; 5178 - 87) developed Markov models to simulate 10
y...
Upfront vs Sequential or Extended
therapy
 An update of Markov model analysis (Cancer 2006; 106:2576-82)
further showed t...
Anastrazole 1st line…
North American Trial andTARGET trial (Tamoxifen and
Anastrazole Randomised Group Efficacy andTolerab...
NCCN, ASCO, ESMO & St Galen Expert Committee
Recommendations
pre & perimenopausal ER+Woman post menopausal ER+ woman
Tamox...
Emerging hormonal therapy sequence
Postmenopausal woman with ER+ Advanced
breast cancer
1st line Tamoxifen AI
2nd line Ful...
Anastrazole as Neo-Adjuvant therapy
Hormone therapy with EBRT
Node negetive ER positive breast ca withT size upto 10 mm(n=1009)
Lumpectomy
Tamoxifen (n=336) X...
Hormone therapy & chemotherapy
 ADVANTAGE- 1. Synergistic effect
2. Inhibition of p-glycoprotein
3. Downregulation of bcl...
Ovarian ablation & suppression
Surgical overian ablation
 First report of surgical oophorectomy for the treatment of
advanced breast cancer published by...
Radiation induced ovarian ablation
Features
• Non invasive &
cheap
• Low dose radiation
• Takes 2-3 months
for effects to ...
Other uses of endocrine therapy in breast
cancer
 Risk reduction in LCIS- NSABP P1 trial and STAR trial
 Use in DCIS- NS...
Questions without answers.....yet
 The use of anastrozole is well established, but we still do not
know if anastrozole is...
Where we stand......for now
 50 % of our patients are Pre-menopausal.
 AIs have no role on them even if they are ER +ve....
Prostate & other hormone responsive cancers….
By Dr. Imran Khan
THANK YOU
Hormone therapy in breast cancer
Hormone therapy in breast cancer
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Hormone therapy in breast cancer

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Hormone therapy in breast cancer

  1. 1. HORMONE THERAPY IN BREAST CANCER By Dr. Rajib Bhattacharjee
  2. 2. Sir George Thomas Beatson “ovaries may be the exciting cause of cancer of breast” Beatson CT. On treatment of inoperable cases of carcinoma of the mamma: suggestions for a new method of treatment with illustrative cases. Lancet1896;2:104–7.
  3. 3. Hormone - definition “A hormone is a class of regulatory biochemical that is produced in all organisms by glands, and transported by the circulatory system to a distant target organ to coordinate its physiology and behavior.” ----wiki
  4. 4. Hormone responsive malignancies Endometrium Prostate Breast
  5. 5. Hormone receptor +ve breast cancer histology-ductal,lobular,mixed,metaplastic (STAGE I-III) HER2neu +ve Node +ve node –ve HT+CT <= 5mm 5-10mm >10mm HT HT +/- CT HT+CT CT includesTrustuzumab HER2neu –ve Node +ve Node –ve HT+CT >5mm <=5mm HT 21 gene RT-PCR assay LRR IRR HRR HT HT+/-CT HT+CT # NCCN
  6. 6. Hormone receptor +ve breast cancer Histology- Tubular, Mucinous (STAGE I-III) node +ve node –ve HT+/- CT <=1cm 1-2.9cm >=3cm Ovb +/-HT HT+/-CT The variation in treatment in early breast cancer & locally advanced breast cancer is loco-regional.The principle of endocrine manipulation is same in these two situations. # NCCN
  7. 7. Hormone receptor +ve breast cancer STAGE IV or recurrent disease No prior HT within 1 yr Prior HT within 1 yr premeno postmeno visc crisis premeno postmeno visc crisis OA/OS/HT HT iCT OA/OS/SERM AI/SERM/SERD iCT progression try upto 3 HT regimens yes CT no clinical benefit symptomatic visc mets no new HTTrials #NCCN
  8. 8. Adjuvant hormone therapy pre-menopausal @ diagnosis post-menopausal @ diagnosis Tamoxifen(5 yrs) / OS / OA AI(5 yrs) AI(2-3 yrs) Tamox(2-3yrs) Tamox(5 yrs) Pre-menopausal post-menopausal No HT AI(5 yrs) tamox(2-3 yrs) AI(2-3 yrs) AI(5 yrs) C/I to AI Tamoxifen (5 yrs) #NCCN
  9. 9. Endocrine therapy surgical radiotherapy hormonal agents Oophorectomy Ovarian ablation
  10. 10. Hormone receptor status & probability of response to therapy ER status PR status Response probability Positive Positive high (50-70%) Positive Negative intermediate(33%) Negative Positive intermediate(33%) Negative Negative low(<10%)
  11. 11. Hormonal agents in breast cancer Class of drug Individual drug dose Route of delivery Frequency of delivary SERM Tamoxifen, Raloxifen, Toremifen 20 mg 60 mg 60 mg Oral Oral Oral OD OD OD Aromatase Inhibitor Anastrazole, Letrozole, Exemestane 1 mg 2.5 mg 25 mg Oral Oral Oral OD OD OD SERD Fulvestrant 500 mg IM Once a month GnRH Analogues Goserelin Leuprolide 3.6 mg 7.5 mg IM IM Once a month Once a month Anti-androgens Bicalutamide 50 mg Oral OD Androgen fluoxymesterone 10 mg Oral BD Progestational agents Megestrol, Medroxyprogesterone acetate Varies Varies Oral Oral / IM OD Varies
  12. 12. SERM 3rd Generation Lasofexifen 2nd Generation Raloxifen 1st Generation Tamoxifen Toremifen
  13. 13. Tamoxifen Mechanism of action  Tamoxifen binds competitively to ER Tamox-ER dimer binds to ER elements nucleus inhibits transcription & signal transduction pathways inhibits cellular growth & proliferation  Tamoxifen TGF beta inhibits TGF alfa & IGF 1 Inhibits cell growth & proliferation
  14. 14. Tamoxifen FDA approved indications  Prevention of premenopausal breast cancer  Treatment of DCIS  Treatment of surgically resected premenopausal ER+ve breast cancer Estrogenic effects  Beneficial effects- decrease in total cholesterol in blood, preservation of bone density in postmenopausal women.  Deleterious effects- hot flushes, vaginal symptoms(dryness, discharge, bleeding), thromboembolic events, Endometrial cancer.
  15. 15. Tamoxifen Drug interactions --Tamoxifen inhibits hepatic P450 system metabolism Warfarin Cyclophosphamide Antidepressants(SSRI/SNRI) Antipsychotics CYP2D6 Tamoxifen Endoxifen (active metabolite) activity ofTamoxifen
  16. 16. Tamoxifen Caution  Vaginal bleeding, pelvic pain refer to gynaecologist  Abnormal liver function drug accumulation toxicity  Thromboembolism or hypercoagulable state  Transient tumor flare  Premenopausal women amenorrhoea Toxicity  Menopausal symptoms  Fluid retention & peripheral edema  Tumor flare  Visual disturbances  Skin rash, pruritus, hair fall  Thromboembolic complications  Endometrial hyperplasia, polyps & endometrial cancer
  17. 17. Tumor flare  Incidence: 4% to 7% with high-dose estrogen 3% to 13% with tamoxifen  Dramatic  in bone pain, an  in size & number of metastatic skin nodules, and erythema.  Within days to several weeks after starting treatment  Hypercalcemia in 5%  Tumor regression may occur as the flare reaction subsides  Look for objective evidence of disease progression if the patient's symptoms have not resolved by 4 to 6 weeks as flare is transient
  18. 18. Contra-indications of Tamoxifen ABSOLUTE  Retinal macular edema or degeneration  H/O benign or malignant liver tumor secondary to oral contraceptives  Pregnancy  Other hormonal treatment or OCP RELATIVE  H/O thrombophlebitis  H/O depression  Cataract  Severe vasomotor symptoms  Polycystic ovaries
  19. 19. Raloxifen Estrogen agonist action Estrogen antagonist action Bone liver breast endometrium Treat osteoporosis cholesterol growth & proliferation NSABP P2Trial compared Raloxifen withTamoxifen advantages disadvantages Lower risk of thrombolic events & endometrial cancer Inferior toTamoxifen in cancer control
  20. 20. Arometase inhibitor Steroidal AI (type 1) Non steroidal AI(type 2) MOA Steroidal AI Binds irreversibly with active site of aromatase enzyme Irreversible enzyme inhibition non steroidal AI reversible bond to the heme iron atom Reversible enzyme inhibition 1st generation Aminoglutethimide 2nd generation Formestane Rogletimide Fadrozole 3rd generation Exemestane Anastrazole Letrozole vorozole
  21. 21. Anastrazole & Letrozole Anastrazole  Bone density measurement needs to be performed prior to initiation of treatment & at regular intervals  No dose adjustments needed in case of renal or hepatic failure  No marked effect on lipid profile  Toxicities-Asthenia(20%), arthralgia(10-15%), hot flashes(10%), peripheral edema(7%)  Advantages- no thrombembolic events no endometrial effects Letrozole  Bone density measurement  Drug interactions- 1. Warfarin – increased PT, INR 2. Clopidogrel- reduce effect  Caution in deranged liver function – dose adjustment  Toxicities- myalgia, arthralgia, hot flushes  Advantages- no thrombembolic events no endometrial effects
  22. 22. SERD-Fulvestrant  MOA- High affinity for ER Downregulates expression of ER  Indications- metastatic hormone receptor positive breast cancer in post menopausal women who have progressed on anti-estrogen therapy  Dose – 500 mg IM on D1, D15, D29 Monthly  Caution – bleeding diathesis, on anticoagulant, thrombocytopenia avoid pregnancy, avoid breast feeding  Toxicities – asthenia (25%),hot flushes(20%),flu like symptoms(10%)
  23. 23. GnRH Analogues Goserelin & Leuprolide  They are used for Medical Ovarian Suppression  MOA- Desensitisation of pituitary to GnRH Secretion of LH & FSH from Pituitary  Dose – Goserelin- 3.6 mg SC every 28 days or 10.8 mg SC every 90 days Leuprolide- 22.5 mg SC every 3 months or 30 mg SC every 4 months  Caution-Transient tumor flare due to initial release of LH & FSH. May occur in upto 20% of patients usually within 1st 2 weeks of starting therapy
  24. 24. Megestrol acetate  MOA- Direct anti-estrogenic effect inhibits LH receptor inhibits stability, availability & turnover of ER  Dose – 160 mg PO/day in advanced breast cancer 320 mg/day in cancer related cachexia 20 - 40 mg/day in hot flushes  Caution – H/O thromboembolic events Diabetes Mellitus Abnormal liver function- dose reduction may be needed Risk of weight gain & fluid retention- SRD  Toxicities- weight gain, thromboembolism, hyperglycemia, breakthrough menstrual bleeding, tumor flare
  25. 25. Antiandrogens Luminal ER-/AR+ Breast cancer  A molecular subtype of breast cancer which is not sensitive to antiestrogens but show an overexpression of Androgen Receptors(AR+)  Increased overexpression of AR is associated with resistance to antiestrogens which act via ERs  Antiandrogen Bicalutamide may be a useful targeted therapy in such situations  Recently Enzalutamide has been studied in vitro and in preclinical models of ER+/- Breast cancer which express AR.This study supports initiation of clinical studies evaluating enzalutamide in AR+ tumors irrespective of ER status Cochrane et al. Breast Cancer Research 2014 16:R7
  26. 26. So many arrows in our repertoire…..which one to shoot…. Tamoxifen for 5 years  41% reduction in the annual rate of breast cancer reccurence  34% reduction in annual death rate for woman with ER +ve breast cancer  Longer and shorter durations of treatment had less impact  Not effective for preventing recurrence in hormone receptor negative breast cancer Early Breast CancerTrialistsGroup. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005;365(9472):1687.
  27. 27. Tamoxifen for how long…? Tamoxifen is recomended for 5 years in our clinical practice Cause – 1. Carry over effect 2. Risk of endometrial cancer increases with longer duration of tamoxifen therapy Trials – 1. In the EBCTSG meta-analysis 5 yr tamoxifen reduced the risk of recurrence and death twice as much as 2 yr tamoxifen therapy. 2.Three trials including one large NSABP trial have compared 5yrs ofTamoxifen treatment with longer treatment- no convincing evidence that treatment lasting longer than 5 years is beneficial. Rather a detrimental effect is seen in longer duration therapy. Two trials investigating these issues- ATLASTrial & ATTOMTrial
  28. 28. To AI or not to AI… that is the problem… Timing / setting Trial AI No. of pt Hazard ratio for DFS Absolute diff in DFS Upfront; y O ATAC BIG1-98 ANZ LET 9366 8010 0.87 0.81 2.8@ 5 yrs 2.6@ 5 yrs Sequential; After 2-3 yrs ofTAM IES ARNO/ABCSG ITA EXE ANZ ANZ 4742 3224 448 0.68 0.60 0.57 4.7@ 3 yrs 3.1@ 3 yrs Extended ; After 5 yrs of TAM MA17 NSABP B33 LET EXE 5187 1598 0.58 0.68 4.6@ 4 yrs 2.0@ 4yrs
  29. 29. How to attack.....?? ATAC Trial ER +ve Breast Cancer in a postmenopausal woman (n=9366) Arimidex Tamoxifen combination 1mg for 5 yrs 20mg for 5 yrs A+T for 5 yrs (n=3125) (n=3116) (n=3125) Median fallow up 68 months Conclusion – Arimidex alone is better than tamoxifen alone. Similar survival in combination arm
  30. 30. A big trial comparing four arms BIG 1-98Trial Post menopausal ER positive breast cancer(n=8010) LTZ for 5 yrs TAM for 5 yrs LTZ for 2 yrs TAM for 2 yrs TAM for 3 yrs LTZ for 3 yrs Median fallow up 28.5 months Conclusion- 4 year DFS significantly higher in favour of Letrozole
  31. 31. ITA- a sequential trial ER+ postmenopausal node positive breast ca(n=448) TAM for 5 yrs TAM for 2-3 yrs ANZ for 3-2 yrs median Follow up- 64 months Event free survival hazard ratio – 0.57 Conclusion –Tamoxifen fallowed by Anastrazole is better thanTamoxifen alone
  32. 32. Mother of all trials...? MA.17Trial Post menopausal, receptor +ve woman, who have completed 4.5 - 6yrs of Tamoxifen and remained disease free LET(5 yrs) Placebo ER+/PR+ 51% reduction in recurrence ER+/PR- 23% reduction in recurrence ER-/PR+ 44% reduction in recurrence Letrozole group showed 42% improvement in OS Conclusion– Addition of Letrozole toTamoxifen has clear benifit over Tamoxifen alone.
  33. 33. Upfront vs Sequential or Extended therapy ITA & ARNO/ABCSGTrials support the benifits of switching from Tamoxifen to Anastrazole but......  Not yet offered long term fallow up analysis  No head to head comparison between upfront Anastrazole vs Switching or Extended therapy  Point at which switching to be done is hitherto undecided In the absence of experimental evidences, these issues have been addressed with the help of computar models.....
  34. 34. Upfront vs Sequential or Extended therapy Punglia et al (JCO 2005; 23; 5178 - 87) developed Markov models to simulate 10 yrs DFS among patients treated with  5 yrs ofTamoxifen The model is based on ...  5 yrs of AI * Available clinical data  Switching to AI after 2.5 or *Assuming all commercially 5 yrs ofTamoxifen availableAIs would have similar efficacy and tolerability Results – Best adjuvent therapy is switching to AI after 2.5 yrs ofTAM With this regimen. Absolute DFS rates at 10 yrs would be 83.7% & 67.6% for node –ve and node +ve patients respectively. Upfront therapy with A yielded rates of 82.6% & 65.5% respectively
  35. 35. Upfront vs Sequential or Extended therapy  An update of Markov model analysis (Cancer 2006; 106:2576-82) further showed that different subpopulation of patients might benefit from different therapeutic regimens :- 1. ER+/PR+ Sequential treatment. 2. ER+/PR- Up-front treatment with AI. 3. Switching to AI after 5 yrs of ‘T’ did not further improve the DFS rates at 10 years. Another computer model analysis proposed by Hilsenbeck et al (Clin Cancer Res 2006; 12:1049-1055) supported the predictions of Markov model.
  36. 36. Anastrazole 1st line… North American Trial andTARGET trial (Tamoxifen and Anastrazole Randomised Group Efficacy andTolerability) Post menopausal ER/PR + Advanced Breast CA Tamoxifen Anastrazole Result – Anastrazole showed greater clinical benefit than Tamoxifen Inference- Anastrazole is the approved 1st line hormonal agent in post menopausal hormone receptor positive breast cancer
  37. 37. NCCN, ASCO, ESMO & St Galen Expert Committee Recommendations pre & perimenopausal ER+Woman post menopausal ER+ woman Tamoxifen Aromatase Inhibitor “Role ofTamoxifen in receptor negative tumor needs further evaluation” Early Breast CancerTrialists Collaborative Group
  38. 38. Emerging hormonal therapy sequence Postmenopausal woman with ER+ Advanced breast cancer 1st line Tamoxifen AI 2nd line Fulvestrant AI Fulvestrant Tamoxifen 3rd line AI Fulvestrant MA Fulvestrant 4th line MA MA Tamoxifen MA #MD ANDERSON CANCER CENTER
  39. 39. Anastrazole as Neo-Adjuvant therapy
  40. 40. Hormone therapy with EBRT Node negetive ER positive breast ca withT size upto 10 mm(n=1009) Lumpectomy Tamoxifen (n=336) XRT (n=336) TAM + XRT(n=337) Results: XRT and placebo resulted in a 49% lower hazard rate of IBTR than didTAM alone; XRT andTAM resulted in a 63% lower rate than did XRT and placebo. When compared withTAM alone, XRT plusTAM resulted in an 81% reduction in hazard rate of IBTR. Conclusion: In women with tumors < 1 cm, IBTR occurs with enough frequency after lumpectomy to justify considering XRT, regardless of tumor ER status, andTAM plus XRT when tumors are ER positive. #J Clin Oncol 20:4141-4149. © 2002 by American Society of Clinical Oncology.  Tamoxifen, Radiation Therapy, or Both for Prevention of Ipsilateral Breast Tumor Recurrence After Lumpectomy in Women With Invasive Breast Cancers of One Centimeter or Less By Bernard Fisher, John Bryant, James J. Dignam, D. Lawrence Wickerham, Eleftherios P. Mamounas, Edwin R. Fisher,Richard G. Margolese, Lois Nesbitt, Soonmyung Paik, Thomas M. Pisansky, and Norman Wolmark for the National Surgical Adjuvant Breast and Bowel Project
  41. 41. Hormone therapy & chemotherapy  ADVANTAGE- 1. Synergistic effect 2. Inhibition of p-glycoprotein 3. Downregulation of bcl-2  DISADVANTAGE- 1. Cytostatic mode of action 2. Calmodulin antagonism  TRIALS – Premenopausal- NSABPTrial- 35% decrease in recurrence Other trials inconclusive The 1995 Oxford meta-analysis showed a significant reduction in recurrence rates and deaths. Postmenopausal- Benefits are less certain Best in node+ve 50-60 yr pt with Doxo NSABP P20, SWOG8814, IBCSGTrial IX  SEQUENCE- INTERGROUP 0100Trial- sequential vs concurrent CT/HT- Improved 8 yr DFS in sequential group
  42. 42. Ovarian ablation & suppression
  43. 43. Surgical overian ablation  First report of surgical oophorectomy for the treatment of advanced breast cancer published by Dr. George Beatson in 1896 who saw a young lactating woman with advanced breast cancer and had tumor regression after removing both her ovaries.  Oophorectomy reliably and promptly reduces circulating estrogens to postmenopausal levels in nearly 100% of women, and has the advantage of simultaneously reducing ovarian cancer risk. It is also the most cost-effective method of ovarian ablation.  But oophorectomy may require hospitalization and carries potential operative and anesthesia-related morbidity and mortality. It also irreversibly induces premature menopause with sequelae including osteoporosis, an increased risk of coronary artery disease and permanent loss of fertility.
  44. 44. Radiation induced ovarian ablation Features • Non invasive & cheap • Low dose radiation • Takes 2-3 months for effects to appear Technique • Position-Supine • Field-Parallel opposed • Energy-Co60/6MV LINAC • Field borders- encompasses entire true pelvis; lower border just below the superior border of symphysis pubis • Field size- 10*15 cm • Dose - 10-12 Gy in 5-6 # Results • The first series was reported by Foveau de Courmellles in 1922 • Treves in 1957 showed that fallowing ovarian irradiation 10 yrs survival improved from 33.8%-42.3% • Benifit was greater in node negative patients
  45. 45. Other uses of endocrine therapy in breast cancer  Risk reduction in LCIS- NSABP P1 trial and STAR trial  Use in DCIS- NSABP B24 trial and UK-DCIS trial  Male breast cancer
  46. 46. Questions without answers.....yet  The use of anastrozole is well established, but we still do not know if anastrozole is superior to other steroidal or non- steroidal AIs.  Some trials have shown the efficacy on Exemestane and Formestane in Anastrozole & Letrozole failure patients.  No direct comparison between up-front use of anastrozole vs. after 2-3 years ofTAM.  Benefits of extended anastrozole adjuvant therapy ?  Long term side effects of AIs ?  NACT converts 10 % receptor +ve tumours into receptor – ve. Is it unidirectional ?
  47. 47. Where we stand......for now  50 % of our patients are Pre-menopausal.  AIs have no role on them even if they are ER +ve.  TAM should be given in ER +ve pre-menopausal patients.  TAM reduces the incidence of contralateral breast cancer even in “ER poor” tumours (EBCTCG meta- analysis).  SERMs have been successful as ‘Chemo-prevention’ in women with ‘High Risk’ for breast cancer.  Incidence ER positivity increases with age & menopausal status. CanTAM may be given in Chemotherapy induced menopausal patients with unknown or –ve ER status ?
  48. 48. Prostate & other hormone responsive cancers…. By Dr. Imran Khan THANK YOU

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