Postmenopausal Hormone Postmenopausal Hormone Therapy and Breast Therapy and Breast Cancer Cancer PHT : an Initiator or PHT : an Initiator or Promoter/Cofactor ? Promoter/Cofactor ? Semih Kaleli Semih Kaleli Cerrahpaşa Medical Faculty Cerrahpaşa Medical Faculty Department of Obstetrics and Department of Obstetrics and Gynecolgy Gynecolgy
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Postmenopausal Hormone Therapy and Breast Cancer PHT : an Initiator or Promoter/Cofactor ? Semih Kaleli Cerrahpaşa Medical Faculty Department of Obstetrics.
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Postmenopausal Hormone Postmenopausal Hormone Therapy and Breast Therapy and Breast
CancerCancer
PHT : an Initiator or PHT : an Initiator or Promoter/Cofactor ?Promoter/Cofactor ?
Semih KaleliSemih Kaleli
Cerrahpaşa Medical FacultyCerrahpaşa Medical Faculty
Department of Obstetrics and GynecolgyDepartment of Obstetrics and Gynecolgy
Collaborative Group Study on PHT and Collaborative Group Study on PHT and Breast CancerBreast Cancer
Prospective studies RRProspective studies RR Canada NBSS 1.01Canada NBSS 1.01 Schairer Schairer NIHNIH 0.97 0.97 NurseNursess’ Health ’ Health 1.201.20 Netherlands’ Cohort 0.98 Netherlands’ Cohort 0.98 Iowa Iowa WomenWomen’s Health 1.20’s Health 1.20 Other 0.62Other 0.62 All Prospective 1.09All Prospective 1.09
Collaborative Group Study
Case-Population ControlledCase-Population Controlled RR RR Brinton 1.09Brinton 1.09 CASH 1.20CASH 1.20 Histop 1.15Histop 1.15 Bain 1.33Bain 1.33 Ewertz 1.35Ewertz 1.35 Long Island 1.49Long Island 1.49 4 state study 1.174 state study 1.17 Yang/Gallagher 1.29Yang/Gallagher 1.29 Stanford 0.75Stanford 0.75 Other 0.96Other 0.96 All Case-Population Controlled 1.15All Case-Population Controlled 1.15
Collaborative Group Study
Collaborative Group Study on PHT and Collaborative Group Study on PHT and Breast CancerBreast Cancer
PHT- Stage of Breast CancerPHT- Stage of Breast Cancer
Collaborative Group Study
WHI StudyWHI Study
AimAim: CVD, breast cancer, colorectal cancer and : CVD, breast cancer, colorectal cancer and osteoporotic fracture riskosteoporotic fracture risk
Age 50-80 yrs (64.500+100.000 women)Age 50-80 yrs (64.500+100.000 women) Most expensive NIH study (628 million USD)Most expensive NIH study (628 million USD) 1. Diet1. Diet 2. PHT2. PHT 3. Calcium-VitD3. Calcium-VitD 40 center, started 1993-1998, ended 200740 center, started 1993-1998, ended 2007 2002’ EP Arm stopped and 2004’ E Arm stopped2002’ EP Arm stopped and 2004’ E Arm stopped
Adenocarcinomas 50-150 daysAdenocarcinomas 50-150 days
Some embriyonal tumors 20-40 daysSome embriyonal tumors 20-40 days
If it is assumed that an exponential growth occurs early in the If it is assumed that an exponential growth occurs early in the malignancy and tumor starts from a single cell, malignancy and tumor starts from a single cell,
20-tumor doublings require for the tumor mass to reach 1-mm20-tumor doublings require for the tumor mass to reach 1-mm 30 tumor doublings get the tumor mass up to 1 cm30 tumor doublings get the tumor mass up to 1 cm Some embryonal tumors and lymphomas have shortest Some embryonal tumors and lymphomas have shortest
doubling times such as 20-40 daysdoubling times such as 20-40 days However, adenocancers have relatively longer doubling times However, adenocancers have relatively longer doubling times
that usually range from 50 to 150 daysthat usually range from 50 to 150 days Breast cancers are supposed to have approximately 100 days Breast cancers are supposed to have approximately 100 days
of tumor doubling. Therefore, breast cancers that initiated of tumor doubling. Therefore, breast cancers that initiated after an PHT, needs app. 3000 days (8.2 years) to be able to after an PHT, needs app. 3000 days (8.2 years) to be able to reach to clinically palpable phasereach to clinically palpable phase
Also, premammographic phase needs at least 5 years past to Also, premammographic phase needs at least 5 years past to be able to detect a breast carcinomas be able to detect a breast carcinomas
Tumor Volume Doubling Time of Tumor Volume Doubling Time of Primary Breast Cancer Primary Breast Cancer
Age at geometric mean Age at geometric mean
diagnosis in days 68 % rangediagnosis in days 68 % range
EP 22/150 (15 %) EP 22/150 (15 %) 42/199 (21 %)42/199 (21 %) MWS PHT all breast cancers diagnosed at anMWS PHT all breast cancers diagnosed at an
average of 1.2 yearsaverage of 1.2 years
Tjonneland A et al. Cancer 2004;100:2328–37
Receptor Status of Breast Cancer Receptor Status of Breast Cancer Cases Diagnosed During PHTCases Diagnosed During PHT
Tjonneland A et al. Cancer 2004;100:2328–37
Changes of Proliferation Markers in Changes of Proliferation Markers in Breast Cancer Developed During PHTBreast Cancer Developed During PHT
Prasad. Cancer 2003;98:2539–46
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Holmberg L. THE LANCET • Vol 363 • February 7, 2004
HABITS Study: New Tm in Breast HABITS Study: New Tm in Breast Cancer Patients During PHTCancer Patients During PHT
Prevelance of Occult Breast Cancer in Prevelance of Occult Breast Cancer in Healthy WomenHealthy Women
Age Group BC Age Group BC
20-54 21 % Breast Cancer 20-54 21 % Breast Cancer 18 % in situ BC18 % in situ BC 14 % DCIS14 % DCIS 4 % LCIS4 % LCIS 1 % DCIS+LCIS1 % DCIS+LCIS 40-50 39 % BC40-50 39 % BC
Nielsen M et al. Br J Cancer 1987;56:814–819
By the time that the slowest growing breast tumor has become 2 cm, there are many more invasive tumors
in the population as well as undiscovered DCIS
SummarySummary
Postmenopausal EP use slightly increases the Postmenopausal EP use slightly increases the breast cancer risk after 4-5 years. breast cancer risk after 4-5 years.
Postmenopausal estrogen-only HT is safe at Postmenopausal estrogen-only HT is safe at least 7-8 yearsleast 7-8 years
Prior HT does not change the current risk of Prior HT does not change the current risk of breast cancer attributable to PHTbreast cancer attributable to PHT
Acceleration/promotion of Acceleration/promotion of preexisting/undiscovered breast tumors by PHT preexisting/undiscovered breast tumors by PHT is not certain but it is possibleis not certain but it is possible
Screen detected and interval breast cancer during PHT
Norwegian breast cancer screening program
Hofvind S et al. Int J Cancer 2006;118,3112–3117
EP Use and Mammographic DensityEP Use and Mammographic Densityin Postmenopausal Women:in Postmenopausal Women:
WHI Study WHI Study
density change EP (%) Placebo (%)density change EP (%) Placebo (%) Year 1-baseline 6.0 -0.9 Year 1-baseline 6.0 -0.9 (4.6:7.5) (-1.5:-0.2)(4.6:7.5) (-1.5:-0.2) Year 2-baseline 4.9 -0.8Year 2-baseline 4.9 -0.8 (3.6:6.3) (-1.6:-0.1)(3.6:6.3) (-1.6:-0.1)
McTiernan A et al. J Natl Cancer 2005;1366-76
Value of the Breast Imaging Value of the Breast Imaging TechniquesTechniques
n=429,000, 43 facilities, 2351 BC casesn=429,000, 43 facilities, 2351 BC cases
25-50 % of cases of BC are identified retrospectively on 25-50 % of cases of BC are identified retrospectively on the previous annual screening mammographythe previous annual screening mammography