The combined incidence and the extended disease course of breast and prostate cancer is a major challenge for health care systems. The solution for society requires an economically viable treatment strategy to maintain individuals disease free and productive, so as to avoid the fracture of the family unit. Forty years ago, translational research using the antiestrogen tamoxifen was targeted to estrogen receptor (ER) positive micrometastatic tumor cells and established the long-term antihormone adjuvant treatment strategy used universally today. The antihormone strategy was the accepted structure of cancer biology. Sex steroid deprivation therapy remains the orthodox strategy for the treatment of both breast and prostate cancer. Despite major initial therapeutic success, the strategies of long term anti-hormone therapies with either tamoxifen or aromatase inhibitors (AI) or antiandrogens or abiraterone for breast and prostate cancer, respectively, eventually lead to a significant proportion of anti-hormone resistant or stimulated tumor growth. Remarkably, a general principle of anti-hormone resistance has emerged for both breast and prostate cancer based primarily on clinical and supportive laboratory data. Paradoxically, anti-hormone resistant cell populations emerge and grow but are vulnerable to the cytotoxicity of estrogen or androgen-induced apoptosis for both breast and prostate cancer, respectively. These consistent anticancer actions of sex steroids appear to recapitulate the more complex mechanism of bone remodeling in elderly men and women during sex steroid deprivation. Estrogen is the key hormone in both sexes because in men androgen is first converted to estrogen. Estrogen regulates and triggers apoptosis in osteoclasts that develop during estrogen deprivation and destroy bone to cause osteoporosis. Sex steroid deprived breast and prostate cancer has recruited a streamlined natural apoptotic program from the human genome, but this is suppressed in the majority of sex steroid deprived tumors. Targeted strategies to neutralize cell survival pathways are now required to amplify and enhance sex steroid induced apoptosis. Successful blockade of the critical pathways for cell survival will introduce an inexpensive targeted therapy to maintain breast and prostate cancer patients indefinitely. Rotating anti-hormonal and sex steroid targeted cocktails could maintain patients at a microscopic tumor burden to enhance the quality of life, enhance survival, and maintain the family as a self-supporting and economically productive unit within society.