Breast tenderness and breast cancer risk in the estrogen plus progestin and estrogen-alone women’s health initiative clinical trials

Crandall, Carolyn J.; Aragaki, Aaron K.; Cauley, Jane A.; McTiernan, Anne; Manson, JoAnn E.; Anderson, Garnet L.; Chlebowski, Rowan T.

doi:10.1007/s10549-011-1848-9

Cited by 56 publications

(38 citation statements)

References 42 publications

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“…The past 50 years has seen the rise and fall of hormone replacement therapy (HRT) [191,199,200] as the answer to postmenopausal women's health (Fig. 5).…”

Section: Discussionmentioning

confidence: 99%

A New Therapeutic Paradigm for Breast Cancer Exploiting Low Dose Estrogen-Induced Apoptosis

Jordan¹

2013

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATEJune PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Georgetown University PERFORMING ORGANIZATION REPORT NUMBERWashington, DC 20057-0004 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel CommandFort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTThe purpose of the CoE is to discover the molecular mechanisms and the modulation estrogen-induced apoptosis. The laboratory research project is focused on genomics and proteomics with a current focus on molecular interrogation to decipher mechanisms that may be applied to aid patient treatment. In parallel, but not supported by the CoE, is a pilot clinical study of estrogen-induced apoptosis in patients with metastatic breast cancer, that have had repeated cycles of successful antihormone therapy, but have subsequently failed and relapsed. A new low dose protocol is being completed. The molecular pharmacology laboratory of the Principle Investigator (PI) is advancing in all areas originally designated in the grant, e.g. a description of the time dependent changes in estrogen-responsive growth and apoptosis in model cell lines, an evaluation and description of the early proteomic pathways associated with estrogen-induced apoptosis dependent on the estrogen receptor (ER) co-activator AIB1 (SRC-3), the critical importance of the shape of the ER complex, the mechanism of c-Src activity that mediates apoptosis and the genomic spectrum of our endocrine resistant cell lines to define cell sensitivity to estrogen-induced apoptosis. We have discovered and described all the stages of the development of estrogen induced apoptosis through the (mitochondrial) pathway that becomes reinforced by the extrinsic (death receptor) pathway. We have correlated rises in reactive oxygen species (ROS) with intrinsic apoptosis and through RNAseq analysis, identified AP-1 (cFos and cJun) as the critical mediators for estrogen-induced apoptosis. SUBJECT TERMS-Gene expression micr...

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“…The past 50 years has seen the rise and fall of hormone replacement therapy (HRT) [191,199,200] as the answer to postmenopausal women's health (Fig. 5).…”

Section: Discussionmentioning

confidence: 99%

A New Therapeutic Paradigm for Breast Cancer Exploiting Low Dose Estrogen-Induced Apoptosis

Jordan¹

2013

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“…Since women in the WHI study had on average higher body mass index than women in the Million Women Study, this contributes to an explanation of the difference in overall findings for oestrogen-only therapy and breast cancer risk in these two landmark studies [47]. The relationship between HRT and breast cancer risk is thus complex and varies with age at menopause, age at initiation of hormone therapy, anthropometric measures, and other breast cancer risk factors [47,[52][53][54][55]. Moreover, there is no clear consensus about when to discontinue HRT, if started at normal menopause [32][33][34][35].…”

Section: Menopausal Hormone Therapymentioning

confidence: 99%

European Code against Cancer 4th Edition: Medical exposures, including hormone therapy, and cancer

Friis

Kesminiene

Espina

et al. 2015

Cancer Epidemiology

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The 4th edition of the European Code against Cancer recommends limiting - or avoiding when possible - the use of hormone replacement therapy (HRT) because of the increased risk of cancer, nevertheless acknowledging that prescription of HRT may be indicated under certain medical conditions. Current evidence shows that HRT, generally prescribed as menopausal hormone therapy, is associated with an increased risk of cancers of the breast, endometrium, and ovary, with the risk pattern depending on factors such as the type of therapy (oestrogen-only or combined oestrogen-progestogen), duration of treatment, and initiation according to the time of menopause. Carcinogenicity has also been established for anti-neoplastic agents used in cancer therapy, immunosuppressants, oestrogen-progestogen contraceptives, and tamoxifen. Medical use of ionising radiation, an established carcinogen, can provide major health benefits; however, prudent practices need to be in place, with procedures and techniques providing the needed diagnostic information or therapeutic gain with the lowest possible radiation exposure. For pharmaceutical drugs and medical radiation exposure with convincing evidence on their carcinogenicity, health benefits have to be balanced against the risks; potential increases in long-term cancer risk should be considered in the context of the often substantial and immediate health benefits from diagnosis and/or treatment. Thus, apart from HRT, no general recommendations on reducing cancer risk were given for carcinogenic drugs and medical radiation in the 4th edition of European Code against Cancer. It is crucial that the application of these measures relies on medical expertise and thorough benefit-risk evaluation. This also pertains to cancer-preventive drugs, and self-medication with aspirin or other potential chemopreventive drugs is strongly discouraged because of the possibility of serious, potentially lethal, adverse events.

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“…Terapia E-P (CEE + MPA) podwoiła ryzyko raka sutka u kobiet z wyjściową (T 0 ) TS (HR 2,16; 95% CI 1,29-3,74), miała zaś mniejszy wpływ na ryzyko raka u kobiet bez wyjściowej TS (HR 1,17; 95% CI 0,97-1,41). Okazało się także, że nowo powstała TS ma związek ze zwiększonym ryzykiem raka sutka u kobiet stosujących CEE + MPA (HR 1,33; 95% CI 1,02-1,72; p = 0,03), u kobiet stosujących tylko CEE ryzyko nie wzrosło (HR 0,98; 95% CI 0,62-1,53) [36].…”

Section: Charakterystyka Zmian Hormonalnych Okresu Przedmenopauzalnegounclassified

Mastalgia: a serious problem of women at premenopausal age

Pertyński¹,

Stachowiak²

2013

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StreszczenieMastalgia jest częstym objawem zgłaszanym przez kobiety w okresie przedmenopauzalnym. Mając na uwadze jej związek z cyklem miesiączkowym, typowo wyróżnia się mastalgię cykliczną i niecykliczną. Poniższy artykuł charakteryzuje zmiany hormonalne zachodzące w okresie przedmenopauzalnym i ich wpływ na występowanie bólów piersi. Autorzy podkreślają, że przed rozpoczęciem leczenia farmakologicznego koniecznie należy wykluczyć obecność zmian nowotworowych sutka. Leczenie mastalgii to, poza farmakoterapią, również zmiany w stylu życia kobiet oraz psychoprofilaktyka. Szczególną uwagę zwrócono na znaczenie progestagenów w leczeniu mastalgii, w tym na ich potencjalny związek z ryzykiem raka sutka. Problemem pozostaje również stosowanie terapii hormonalnej okresu menopauzy (menopausal hormone therapy -MHT) u kobiet z mastalgią, a decyzja o rozpoczęciu (i kontynuacji) tej terapii winna być każdorazowo podejmowana indywidualnie, po konsultacji z pacjentką.Słowa kluczowe: mastalgia, okres przedmenopauzalny, progestageny, MHT. SummaryMastalgia is a frequent premenopausal symptom. Given the influence of the menstrual cycle, cyclical and non-cyclical mastalgia are typically distinguished. This article describes hormonal changes occurring during the premenopausal period and their influence on breast pains. The authors underline that prior to the onset of pharmacological treatment, any breast cancer lesions should be excluded. The treatment of mastalgia includes also female life-style changes as well as some psychoprophylactic actions. Special attention was paid to progestogens, including their potential relation to the breast cancer risk. Administration of MHT in mastalgia women remains an unsolved issue; a decision to start (or continue) this therapy should be each time made on a caseby-case basis, following the patient's consultation.

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Breast tenderness and breast cancer risk in the estrogen plus progestin and estrogen-alone women’s health initiative clinical trials

Cited by 56 publications

References 42 publications

A New Therapeutic Paradigm for Breast Cancer Exploiting Low Dose Estrogen-Induced Apoptosis

A New Therapeutic Paradigm for Breast Cancer Exploiting Low Dose Estrogen-Induced Apoptosis

European Code against Cancer 4th Edition: Medical exposures, including hormone therapy, and cancer

Mastalgia: a serious problem of women at premenopausal age

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