Breast and Prostate Cancers: A Comparison of Two Endocrinologic Malignancies

Introduction

Prostate and breast cancers are two common malignancies that have some striking and surprising similarities. As we know, they are both tumors of accessory sex organs and both are characterized primarily by being epithelial, hormone-driven malignancies, which respond to so-called “endocrine therapy.” They constitute the second leading cause of cancer-related mortality in the United States for men and women, respectively. In both cancers, there is often a latency period spanning many years from the time of diagnosis of the primary tumor to the development of metastasis. Recent research has revealed that both breast and prostate cancer are complex and heterogeneous disease processes that encompass multiple pathologies with variable treatment options, as opposed to one distinct disease with a uniform treatment. A great deal of experimental and clinical research has been undertaken for each of these cancers resulting in many new strategies of care. Until recently, this has been truer for breast cancer than for prostate cancer. This is partly due to the fact that breast cancer was recognized centuries before prostate cancer, and that it is a more accessible organ. More important reasons are the early vigorous advocacy of breast cancer survivors for research support and the misconception that prostate cancer was an “old man’s disease” meriting little concern. More recently, support for and progress in prostate cancer research has greatly expanded.

Therefore, it seems appropriate now to further explore some of the interesting parallels between these two cancers in addition to some of the differences and areas of ignorance. It is hoped that this comparison will highlight important areas for further inquiry.

History

The earliest descriptions of breast cancer can be traced back to ancient Egypt around 1500 BCE. At that time, it was treated locally with cauterization techniques, but there was no concept of metastatic disease and prognosis was obviously poor. The first mastectomy was performed as early as 548 AD and the first radical mastectomy was performed in the seventeenth century in France, after physicians developed a better understanding of the human anatomy. In 1882, William S. Halstead performed the first radical mastectomy in the United States, and this became the standard of care for all suspicious breast lumps until the mid-1970s. Although the surgery was morbid and later deemed excessive, it improved both staging and long-term survival significantly. With a better understanding of the endocrinological background of breast cancer came the idea of castration (i.e., removing estrogen). In 1889, a German physician named Albert Schinzinger proposed oophorectomy as a treatment for breast cancer. Hypophysectomy was also used for a time to target the hypothalamo-pituitary axis. These endocrine approaches resulted in dramatic, though mostly temporary, remissions.

Prostate cancer was recognized much later and was first described in 1853. Removal of the entire gland and seminal vesicles to treat cancer was not performed until 1904 by Hugh Hampton Young, who used a perineal approach. Gradually, the retropubic approach for radical prostatectomy became safer, and thanks in large part to the work of Patrick Walsh, beginning around 1983, it became the predominant approach for this surgery. A major advantage of this approach was that the pelvic lymph nodes could simultaneously be removed for staging and possibly improved survival. Charles B. Huggins introduced the idea of castration (i.e., removing testosterone) to treat metastatic prostate cancer; a discovery that would earn him the Nobel Prize in 1966. Castration was accomplished either by orchiectomy or the use of estrogen to oppose testosterone. Here again, the responses to castration were dramatic though often temporary. Parenthetically, Huggins et al. also popularized the use of oophorectomy (and adrenalectomy) for breast cancer. The gonadotropin-releasing hormone receptor was later discovered by Andrew Schally, and then agonists and later antagonists were developed and are now the predominant form of castration for prostate cancer. These discoveries earned Andrew Schally the Nobel Prize in 1977.

Epidemiology

Prostate and breast cancers have remarkable epidemiologic parallels, which may hint at an underlying genetic or environmental link. Thanks to the widespread adoption of screening, they are the two most commonly diagnosed cancers in the United States with an estimated 233,000 and 232,670 incident cases of prostate cancer and breast cancer (in women), respectively, in 2014 alone. These two cancers are also the second leading cause of cancer-related deaths in the United States, with 40,000 deaths attributable to breast cancer in women and 29,480 to prostate cancer in 2014. According to statistics from the American Cancer Society, between 2008 and 2010, US men had a one in seven chance of developing prostate cancer during their lifetime, while women had a one in eight chance of developing breast cancer. The reasons for this current incidence and the controversies surrounding it will be discussed in the subsequent section on screening.

Important epidemiological data have been gathered from autopsy studies. Such studies were considerably more difficult to perform in the case of breast cancer, given the larger volume and fatty composition of the organ (averaging hundreds of paraffin blocks per specimen). A compilation of the most important studies from the 1980s revealed the prevalence of asymptomatic invasive and in situ disease to be 1.3 and 8.9%, respectively. Autopsy studies of the prostate revealed a much higher occurrence of the disease in aging men. Almost 60% of men aged 90 or greater were found to have incidental prostate cancer on autopsy. These significant differences found on autopsy might be partially explained by a less detailed pathological analysis of breast tissue and a greater number of autopsies being performed on postmenopausal women, thereby possibly causing some cancers to regress. These provisos notwithstanding, the prevailing evidence suggests that autopsy cancer in breast is much less common than prostate cancer. Why this should be the case deserves further investigation.

In terms of race, prostate and breast cancers have higher mortality rates among African-Americans. African-American men are more likely to be diagnosed with and to die of their prostate cancer while African-American women are less likely to be diagnosed with breast cancer than their Caucasian counterparts, but are more likely to die of their disease. Asians have the lowest mortality rates for both cancers ( Table 19.1 ), but these rates do increase after relocation to Western countries.

Risk factors

Virtually all experts believe that breast and prostate cancers occur because of the interaction of a variety of environmental factors and genetic susceptibility. In breast cancer, the most important risk factor is probably family history and thus genetic predisposition. So-called hereditary breast cancer accounts for 5–10% of all breast cancers and the relative risk increases with the number of first-degree relatives with the disease.

The best known genetic susceptibility factors are mutations in the tumor suppressor genes BRCA1 and BRCA2 , which are responsible for as much as 80% of cases of inherited breast cancer. These mutations confer a lifetime risk of breast cancer of 60–85%, and interestingly, a lifetime risk of ovarian cancer of 15–40%. Mutations in the BRCA2 gene have been found in several nonbreast cancers, including cancer of the prostate. In fact, in 1999 a study by the Breast Cancer Linkage Consortium found a relative risk of 4.65 for prostate cancer in families with BRCA2 mutations.

Another important risk factor for breast cancer is prolonged and unopposed exposure to estrogen (early menarche, nulliparity, first live birth after age 30, and delayed menopause). Other risk factors include age, race, smoking, previous breast disease, breast tissue density, radiation exposure, weight, exercise, and alcohol consumption.

Prostate cancer has many of the same risk factors as breast cancer. Like breast cancer, a positive family history is an important risk factor. The relative risk for men with a single first-degree relative with prostate cancer increases by a factor of 2.1–2.8, and having a first-degree and a second-degree relative with prostate cancer can increase the risk by up to four- to sixfold when compared to the general population. Unfortunately, intensive studies have not yet revealed any genes that have the predictive power of BRCA1 and BRCA2 . However, some experts believe that in subtle, yet-to-be-discovered ways, heredity genes influence both breast and prostate cancer development and progression in as much as 40% of cases.

Also, like breast cancer, it seems that prolonged exposure to steroid hormones, specifically in this case androgens, is an important risk factor for prostate cancer. This fact is evidenced by the elimination of prostate cancer risk in men who undergo early castration or have genetic defects blocking androgen synthesis. Other risk factors for prostate cancer include age, high-fat and low-fiber diet, obesity, and prostatic inflammation.