The sex hormone system in carriers of BRCA1/2 mutations: a case-control study

Widschwendter, Martin; Rosenthal, Adam N.; Philpott, S. J. F.; Rizzuto, Ivana; Fraser, Lindsay; Hayward, Jane; Intermaggio, Maria P.; Edlund, Christopher K.; Ramus, Susan J.; Gayther, Simon A.; Dubeau, Louis; Fourkala, Evangelia Ourania; Zaikin, Alexey; Menon, Usha; Jacobs, Ian

doi:10.1016/s1470-2045(13)70448-0

Cited by 101 publications

(97 citation statements)

References 25 publications

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“…Relative loss of PRB is seen with the development of atypia or malignancy and in women with germline mutations in BRCA1 or BRCA2 (Mote et al 2002). Interestingly, women with such mutations have double the serum progesterone levels compared to age matched WT controls although the significance of this finding is not known (Widschwendter et al 2013). …”

Section: Progesterone and Bcscsmentioning

confidence: 99%

The role of steroid hormones in breast cancer stem cells

Simões¹,

Alférez²,

Howell³

et al. 2015

Endocrine-Related Cancer

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Breast cancer stem cells (BCSCs) are potent tumor-initiating cells in breast cancer, the most common cancer among women. BCSCs have been suggested to play a key role in tumor initiation which can lead to disease progression and formation of metastases. Moreover, BCSCs are thought to be the unit of selection for therapy-resistant clones since they survive conventional treatments, such as chemotherapy, irradiation, and hormonal therapy. The importance of the role of hormones for both normal mammary gland and breast cancer development is well established, but it was not until recently that the effects of hormones on BCSCs have been investigated. This review will discuss recent studies highlighting how ovarian steroid hormones estrogen and progesterone, as well as therapies against them, can regulate BCSC activity.

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Section: Progesterone and Bcscsmentioning

confidence: 99%

The role of steroid hormones in breast cancer stem cells

Simões¹,

Alférez²,

Howell³

et al. 2015

Endocrine-Related Cancer

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show abstract

“…Although the majority of BRCA1 tumours are estrogen receptor negative [4], oophorectomy [5] and tamoxifen [6] have been shown to reduce the risk of breast cancer, while oral contraceptive use increases the risk [7]. Interestingly, a recent study reported higher levels of serum estradiol and progesterone during the median luteal phase in premenopausal BRCA1/2 mutation carriers compared with premenopausal non-carriers, suggesting an important role of sex hormones in their predisposition to cancer [8].…”

Section: Introductionmentioning

confidence: 99%

The effect of oral 3,3′-diindolylmethane supplementation on the 2:16α-OHE ratio in BRCA1 mutation carriers

et al. 2015

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Hormonal exposures are known to influence breast cancer risk among women with a BRCA1 mutation. Thus, dietary factors that increase the 2-hydroxyestrone (OHE):16α-OHE ratio, a biomarker inversely related to breast cancer development, may also influence cancer risk. We conducted a dietary intervention study to evaluate the ability of 300 mg/day of 3,3'-diindolylmethane (DIM) to increase the urinary 2:16α-OHE ratio in 20 women with a BRCA1 mutation. BRCA1 mutation carriers (n = 15) were assigned to receive 300 mg/day of Rx Balance BioREsponse DIM for 4-6 weeks (intervention group) and five BRCA1 mutation carriers did not take DIM (control group). The urinary 2:16α-OHE ratio was assessed at baseline and after 4-6 weeks by immunoassay. There was no significant effect of DIM on the 2:16α-OHE ratio (2.4 at baseline vs. 3.0 after the intervention, P = 0.35). A short dietary intervention with DIM did not significantly increase the 2:16α-OHE ratio in female BRCA1 mutation carriers. Larger studies investigating the effect of dietary or lifestyle interventions on circulating hormone levels in these high-risk women are warranted.

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“…Second, unlike other studies, we only evaluate serum E2 level in the early follicular phase. Only basal E2 level measured on menstrual cycle days 2-5 has been validated as a standardized value [40], and late follicular or luteal phase E2 varies significantly based on individual variation and cycle length, limiting utility of the test outside the early follicular window [41]. A recent case-control study in cancer-free BRCA 1/2 mutation carriers found that luteal phase-not follicular phase-estradiol level is significantly higher in BRCA mutation carriers compared to non-carriers [42].…”

Section: Discussionmentioning

confidence: 99%