Recent studies have found that continuing estrogen into menopause may help decrease cancer risk for certain individuals with an inherited genetic mutation known as the KRAS-variant.1,2,3
However, HRT’s use decreased dramatically after the 2002 Women’s Health Initiative Study reported an association between HRT and worse health outcomes, including increased breast cancer risk.
Over the last decade, researchers have determined that HRT is not a “one size fits all” solution but that it has many benefits, including decreasing breast cancer risk for certain subgroups of women. These findings are summarized in the North American Menopause Society’s 2012 position paper on HRT.
Consistent with these findings, a recent MiraKind study showed that estrogen withdrawal, which occurs after oophorectomy (the removal of both ovaries), with the discontinuation of HRT, or at menopause, may increase cancer risk in women with the KRAS-variant.1 These findings indicate continuing estrogen with HRT may be beneficial for women with the KRAS-variant in these settings, if not otherwise contraindicated.
The KRAS-variant is an inherited genetic mutation associated breast cancer,1 ovarian cancer,4 lung cancer,5 as well as other cancers,6,7 and multiple cancers in the same individual.8,9
If you are considering a pre-menopausal oophorectomy or are peri-menopausal, learning whether you have the KRAS-variant can help you make the important decision about whether or not HRT is right for you.
The MiraKind community brings together individuals with the KRAS-variant to share their stories, learn from one other, and offer support. Learn more.
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- McVeigh TP, Jung SY, Kerin MJ, Salzman DW, Nallur S, Nemec AA, Dookwah M, Sadofsky J, Paranjape T, Kelly O, Chan E, Miller N, Sweeney KJ, Zelterman D, Sweasy J, Pilarski R, Telesca D, Slack FJ, Weidhaas JB. (2015). Estrogen withdrawal, increased breast cancer risk and the KRAS-variant. Cell Cycle. 2015;14(13):2091-9. doi: 10.1080/15384101.2015.1041694. Epub 2015 May 11.
- Cerne JZ, Stegel V, Gersak K, Novakovic S. (2012). KRAS rs61764370 is associated with HER2-overexpressed and poorly-differentiated breast cancer in hormone replacement therapy users: a case control study. BMC Cancer. 2012 Mar 22;12:105. doi: 10.1186/1471-2407-12-105.
- Cerne JZ, Pohar-Perme M, Cerkovnik P, Gersak K, Novakovic S. (2015). Functional variants in CYP1B1, KRAS and MTHFR genes are associated with shorter telomere length in postmenopausal women. Mech Ageing Dev. 2015 Jul;149:1-7. doi: 10.1016/j.mad.2015.05.003. Epub 2015 May 15.
- Paranjape, T., Heneghan, H., Lindner, R., Keane, F., Hoffman, A., Hollestelle, A., Dorairaj, J., Geyda, K., Pelletier, C., Nallur, S., et al. (2011). A 3'-untranslated region KRAS variant and triple-negative breast cancer: a case-control and genetic analysis. Lancet Oncology 12, 377-386.
- Ratner, E., Lu, L., Boeke, M., Barnett, R., Nallur, S., Chin, L., Pelletier, C., Blitzblau, R., Tassi, R., Paranjape, T., et al. (2010). A KRAS-variant in Ovarian Cancer Acts as a Genetic Marker of Cancer Risk. Cancer Research 15, 6509-6515.
- Chin, L., Ratner, E., Leng, S., Zhai, R., Nullur, S., Babar, I., Muller, R., Straka, E., Su, L., Burki, E., et al. (2008). A SNP in a let-7 microRNA complementary site in the KRAS 3' untranslated region increases non-small cell lung cancer risk. Cancer Res 68, 8535-8540.
- Kazmi HR, Chandra A, Kumar S, Satyam LK, Gupta A, Nigam J, Srivastava M, Mittal B. (2016) A let-7 microRNA binding site polymorphism in the KRAS 3’UTR is associated with increased risk and reduced survival for gallbladder cancer in North Indian population. J Cancer Res Clin Oncol. 2016 Sep 12. [Epub ahead of print]
- Gutiérrez-Malacatt H, Ayala-Sanchez M, Aquino-Ortega X, Dominguez-Rodriguez J, Martinez-Tovar A, Olarte-Carrillo I, Martinez-Hernandez A, C CC, Orozco L, Cordova EJ. (2016) The rs61764370 Functional Variant in the KRAS Oncogene is Associated with Chronic Myeloid Leukemia Risk in Women. Asian Pac J Cancer Prev. 2016;17(4):2265-70.