Hot flashes, flushing, and night sweats are known as vasomotor symptoms (VMS), and most often occur in women who are entering or in menopause. VMS are causally related to decreasing estradiol concentrations, mainly in the serum and subsequently also in the temperature regulating center located in the hypothalamus. The lack of estrogen alters neurotransmitter activity, especially in the serotonergic and noradrenergic pathways.
VMS can also be induced (iVMS) by anti-androgen and anti-estrogen cancer therapies and surgical procedures that can lead to treatment non-compliance. 1,2 VMS are caused by low estrogen levels leading to increased stimulatory signaling of NKB on the KNDy neurons in the hypothalamus. A non-hormonal treatment to manage iVMS is needed as estrogen is contraindicated for the management of VMS in patients with hormone-positive tumors, including breast and prostate tumors.
In the study “Factors related to the experience of menopausal symptoms in women prescribed tamoxifen” 3 women with Hormone Receptor positive (HR+) Breast Cancer (CaB) receiving tamoxifen:
- 84% of women experienced hot flashes
- 80% experienced night sweats
- 60% experienced severe symptoms
- Symptoms persisted throughout 5 years of treatment and were mainly attributed to tamoxifen
- After 4.5 years, 46% of women had discontinued tamoxifen
In a prospective analysis of 250 men with HR+ Prostate Cancer (CaP) receiving leuprolide: 4
- 80% of men experience hot flashes
- 15-27% consider hot flashes the most distressing side effect
- 30-40% experienced moderate-to-severe symptoms
- 20% discontinued or disrupted treatment
In women who are breast cancer gene positive (BRCA+) and had bilateral salpingo-oophorectomy (BSO), quality of life analyses conducted post-procedure concluded:
- 67% of women have symptoms of menopause such as hot flashes5
- Up to 35% complain of “extremely bothersome” symptoms up to two years after their surgery6
iVMS are well documented with the use of cancer therapies and certain surgical procedures. Symptoms such as hot flashes can appear immediately and be severe. Cancer therapy side effects can lead to treatment non-adherence which increases the mortality risk and/or shortens the time to recurrence. We believe a treatment for iVMS is needed to help ensure cancer patients are more likely to start and stay on critical cancer therapies.
iVMS Incidence
Table Footnotes:
1 Trinity Partners 2020; 2 Dowsett M, et al., Lancet.386(10001):1341-52, 2015; 3 Lee RJ, et al., Cancer and Chemotherapy and Biotherapy: Principles and Practice. 5th ed; 2011; 4 ACOG Recommendations FAQ505 BRCA1 and BRCA2, August, 2018; 5 Lin J, et al: Cancer Prev Res 2011;4: 1360-1365; 6 Lupron Depot PI March, 2019; 7 Moon, Z. et al., JOURNAL OF PSYCHOSOMATIC OBSTETRICS & GYNECOLOGY, 2017 VOL. 38, NO. 3, 226–235; 8 Challapalli, A, et al., Clinical and Translational Radiation Oncology 10 (2018) 29–35 9 L. Johnson, et al. American Society for Reproductive Medicine, 2014 Vol 102 No. 3, Supplement, e249; 10 Nichols, H, et al., JNCI J Natl Cancer Inst, 2015, 1–8 ; 11 Gonzalez BD et al J Urol 194: 690-695 2015; 12 N Engl J Med. 2002 May 23:346(21):1609-15; 13 Open Med. 2007 Aug 14;1(2):e92-8
References:
- Kotsopoulos J, Huzarski T, Gronwald J, Moller P, Lynch HT, Neuhausen SL, et al. Hormone replacement therapy after menopause and risk of breast cancer in BRCA1 mutation carriers: a case-control study. Breast Cancer Research and Treatment 2016;155(2):365–73.
- Guidozzi F. Hormone therapy after prophylactic riskreducing bilateral salpingo-oophorectomy in women who have BRCA gene mutation. Climacteric 2016;19(5): 419–22.
- Moon, Z. et al., Journal of Pyschosomatic Obstetrics & Gynecology, 2017 VOL. 38, NO. 3, 226–235.
- Challapalli, A, et al., Clinical and Translational Radiation Oncology 10 (2018) 29–35.