Postmenopausal Hormone Therapy-Reduced BC Mortality

Fallleaves

Can't access the entire study. This is just the abstract. Surprisingly, hormone replacement therapy lowered mortality from breast cancer in Finnish women. Doesn't say anything about the effect on incidence of breast cancer, though.

Reduced risk of breast cancer mortality in women using postmenopausal hormone therapy: a Finnish nationwide comparative study.

Objective: Data are controversial on the impact of postmenopausal hormone therapy (HT) on breast cancer mortality. We analyzed nationwide Finnish data on breast cancer mortality risk in women using HT consisting of estradiol-only therapy (ET) or estrogen-progestogen therapy (EPT).

Methods: In total, 489,105 women using HT in 1994 to 2009, traced from the nationwide reimbursement register, were followed from the HT initiation (3.3 million cumulative exposure years) to breast cancer death (n = 1,578 women). The observed deaths were compared with those in the age-standardized background population.

Results: The breast cancer mortality risk was reduced in all HT users with exposure for at most 5 years (standardized mortality ratio 0.56; CI 0.52-0.60), more than 5 to 10 years (0.46; 0.41-0.51), or more than 10 years (0.62; 0.56-0.68). A significantly larger risk reduction was detected in the 50 to 59 years age group (0.33; 0.29-0.37) compared with 60 to 69 (0.64; 0.59-0.70) or 70 to 79 (0.78; 0.69-0.87) years age groups. The death risk reductions in ET users tended to be larger in all age groups compared with EPT users, with a significant difference only in the 70 to 79 years age group (0.66; 0.57-0.76 vs 0.88; 0.77-1.00). The age at HT initiation, regardless whether ET or EPT, showed no association with breast cancer mortality.

Conclusion: In the Finnish unselected population, breast cancer is fatal in 1 of 10 patients. Our data imply that this risk is prevalent in 1 of 20 patients with history of HT use. This is an important message for women considering or already using HT.

http://www.ncbi.nlm.nih.gov/pubmed/27465718

wallycat

Fascinating. Issues with memory aside (wasn't there at least one article somewhere that eluded to women on HRT had higher risk of Alzheimer's/memory problems??) makes me wonder if on/off therapy is better than 5-10 years of any one thing. Especially with an earlier article I posted indicating tumors change depending on therapy. I'm thinking of the new-to-be suggestions of 10 year AI (and for me, personally), I'm thinking on and off and on and off would be better...but hey, I'm no doc.

Fallleaves

Wallycat, yes you are right. The Women's Health Initiative study showed a worsening of cognitive abilities in women who took HRT (not sure if that was estrogen/progestin or just estrogen though). But apparently there have been some other studies that showed a benefit in younger women. This article mentions several studies, but I haven't looked at them yet: http://www.ncbi.nlm.nih.gov/pubmed/27327261

And apparently estrogen-only HRT may have more benefits than harms (at least for younger women). http://www.ncbi.nlm.nih.gov/pubmed/24084921

But timing may have something to do with the effect of estrogen therapy on BC risk, too.

"In a recent update of the Million Women Study, the use of oestrogen-only agents was associated with a 43% increase in the risk of breast cancer (RR 1.43; CI: 1.35–1.51) when treatment had begun less than 5 years after menopause; however, when oestrogen-only therapy was initiated 5 years or more after menopause, there was no influence on breast cancer risk (RR 1.05; CI: 0.89–1.24) [43. A similar tendency was observed in the WHI study; breast cancer risk was reduced among women who first started oestrogen-only therapy 5 years or more after menopause (HR 0.65; CI: 0.48–0.89), whereas the association was close to unity among women who initiated treatment closer to menopause (HR 0.89; CI: 0.66–1.20) [48. Thus, oestrogen-only therapy may be associated with a neutral or increased risk of breast cancer when started close to the time of menopause, but when started later in menopause it may be associated with a neutral or even reduced breast cancer risk [[43]

http://www.cancerepidemiology.net/article/S1877-78...(15)00167-8/fulltext#sec0040

V. Craig Jordan has written some papers regarding the use of estrogen to cause apoptosis of BC cells, but only after 5 year of menopause: "The symmetry of the clinical and laboratory studies now permits the creation of rules for the future clinical application of ERT or phytoestrogen supplements: a 5-year gap is necessary after menopause to permit the selection of estrogen-deprived breast cancer cell populations to cause them to become vulnerable to apoptotic cell death. Earlier treatment with estrogen around menopause encourages growth of ER-positive tumor cells, as the cells are still dependent on estrogen to maintain replication within the expanding population. "

http://www.ncbi.nlm.nih.gov/pubmed/25339261

I've also read other articles indicating it is bad to start HRT more than 10 years after menopause, or to use it for more than 10 years.

I honestly think estrogen is a lot more complicated than we understand. Not only do we have various types of estrogen: estriol, estrone, estradiol, but there are various metabolites that vary in carcinogenicity. And on top of that there are estrogen receptors alpha and beta, and the expression of beta is thought to be protective! I have yet to see a review that ties everything together.

I like your idea about switching things up more frequently. It may be the best way to stay ahead of cancer resistance to treatment.