Estrogen Benefit in Breast Cancer Affirmed
One difference is that the median time to nonadherence to estrogen therapy in the trial was only 3.5 years, which was much shorter than the time noted in studies reporting increased risks, Anderson’s group said.
A benefit is plausible, both groups agreed, if breast cancer cells that developed under low estrogen conditions are inhibited by the change to a higher estrogen environment and vice versa.
In the current analysis, women given estrogen who developed breast cancer were significantly less likely to die from the disease (hazard ratio 0.37, P=0.03) or any cause (HR 0.62, P=0.04). Howell and Cuzick suggested that a withdrawal response may be at work.
“For patients with advanced breast cancer who respond and then progress on high-dose estrogen, stopping of treatment could result in a response (withdrawal response), suggesting that the tumor had adapted to grow at the higher dose,” they said.
Breast cancer is the second most common cancer in women world-wide with 1.05 million new cases being estimated in the year 2001. In developed countries, it is the most common cancer in women. Populations from countries of North America are at high risk of breast cancer, with incidence rates in US white women going up to 103.7 per 100,000. High rates are also reported from Europe and Australia. In the United Kingdom, nearly 30,000 new cases of breast cancer are diagnosed every year with nearly 15,000 deaths reported from this disease.
The incidence rate of breast cancer has been rising both in the developed and developing countries and it is becoming frequent in some developing countries like Egypt and Tunisia. Carcinoma breast is the second most common cancer among Indian women, and an increasing trend in its incidence has been observed in most of the metropolis with Mumbai toping the list.
Sex-hormones have been implicated in various human cancers such as endometrial cancer, breast and prostatic cancer (among sex-organ related neoplasm) or colon cancer, gall-bladder cancer, kidney cancer, etc.( non sex-organ related neoplasm). However, the association between estrogen and breast cancer assumes special significance since breast cancer represents an enormous public health problem. Breast cancer risk is enhanced by increasing the duration of exposure to endogenous ovarian hormones, so early menarche or late menopause increases the risk. Further, the risk of breast cancer is directly related to the age at which women bear first child. An early first, full-term pregnancy seems to have a protective effect. Women whose first pregnancy is delayed to their late 30s are at a higher risk than multiparous women. Unmarried women tend to be at a higher risk than married women.
Further, nulliparity increases and high parity decreases the risk of breast cancer, at least after the age of 50. Nevertheless, the endocrine mechanisms concerning pregnancy and risk of breast cancer are poorly understood. Exogenous hormonal factors such as estrogen replacement therapy and combined oral contraceptive use may cause a small increase in the risk for breast cancer.
Withdrawal responses might explain the improved prognosis of women who developed breast cancer while receiving estrogen therapy, and previous reports have linked withdrawal responses to therapy cessation and extended remission, they added.
Overall, the WHI estrogen trial included more than 10,000 women, ages 50 to 79, without a uterus. They were randomized to 0.625 mg per day of oral conjugated equine estrogen or placebo.
While the trial was stopped early over elevated stroke risk, follow-up continued until the scheduled end date, and an extended surveillance period that included 7,645 women.
Whereas the stroke and other risks faded after the intervention, the reduced incidence of breast cancer with estrogen therapy persisted without a difference between the intervention phase and the postintervention phase (HR 0.79 and 0.75, respectively, P=0.76).