Male Breast Cancer and Hyperestrogenemia: A Thirteen-Year Review

Male breast cancer (MBC) is a very rare malignancy and accounts for 0.1% of all male cancers. MBC has not been studied as extensively as its female counterpart. Certain clinical and pathological risk factors like smoking history, age at onset, family history of cancer, obesity, ethnicity, estrogen/progesterone receptor status and BRCA gene mutation status have all been studied well in the female breast cancer (FBC) patients and the clinical trial evidence from these studies is then extrapolated to treat and manage patients with MBC. One such area of interest is high levels of estrogen and its relationship with MBC. In our retrospect research study we aim to find an association between MBC and high levels of circulating estrogen at the time of diagnosis.

A 13-year retrospective review of the male breast cases at University of Florida College of Medicine's Tumor Registry was conducted. Data regarding certain clinic-pathological risk factors and MBC were collected and reviewed. Main surrogate indicators for elevated estrogen were examined, namely, low HDL (< 40 mg/dL), low albumin (< 4 g/dL) and high BMI (> 25). Presence of any one of these surrogates was seen as an indirect marker for high estrogen level. For cancer staging, the American Joint Committee on Cancer (AJCC) staging system was used. Stages 0-2 were grouped together as they are less extensive compared to stages 3-4 (also grouped together) which represent extensive disease. Univariate analysis was conducted using STATA 13 to do Fischer's exact test as cross-tables showed cell counts of five or less. The main comparison was that between extensive MBC (stages 3-4) and non-extensive breast cancer (stages 0-2).

Between January 2000 and November 2013, we found a total of 2,129 cases of breast cancer patients at our institute. Out of these 2,113 (99.24%) were female and 16 (0.75%) were men. Four MBC patients were excluded because their complete charts could not be found in the medical records department. Six (50%) patients had one indicator, four (33%) patients had two indicators and one (8.3%) patient had all three. Eleven (91.6%) patients had precursors suggestive of hyperestrogenemia. Only one (8.33%) patient did not have any surrogate marker indicator of high estrogen levels. Two (16%) were black and 10 (83.33%) were white. Mean age was 61.75. Five (41%) had a first degree relative with a malignancy. Laterality was nine (75%) in the left breast, three (35%) in right breast. Eight (66.6%) found a mass on physical exam. Five (41.6%) had a positive smoking history. One patient had no data in the chart. Remaining all 11 (91.6%) had non-TNBC. One patient did not have complete documentation. Five (41.6%) had mastectomy, six (50%) received RT, four (33.3%) received chemotherapy and another four received hormone therapy. In terms of stage, four (33.3%) had stage 4, two (16.6%) stage 3B, two (16.6%) stage 2B, two (16.6%) stage 2A, one (8.33%) had stage 1C and one had stage 0. HDL data were available in seven (58.3%) with mean of 37, albumin in 10 (83.3%) with mean of 3.61, BMI in 11 (91.66%) patients with a mean of 33.30. Within subgroups, two patients were black and 10 white. Both black patients had LE disease (stage 0-2). Of the white patients, four (40%) had limited disease while six (60%) had extensive breast cancer. Family history assumed a similar distribution as three (60%) of patients with negative family history for cancer had limited disease and two (40%) had extensive one, same numbers applied for family-history-positive population. Three (60%) of patients with limited disease smoker and two (40%) did not. As for laterality, a total of nine patients had left-sided breast cancer, of whom five had had limited disease and four fell into the extensive disease category. The hormonal status for most patients were HER/NEU negative (seven out of 10 patients, two patients did not have this information on file), ER positive (11 out of 12) and PR positive (8 out of 12). Estrogen status: Low HDL was seen in three out of seven patients, low albumin in four out of 10 and obese BMI in nine out of 11. Finally, 11 out of 12 patients had at least one indicator of high estrogen. No significant change in prevalence of these markers was seen when comparing patients with limited and extensive disease.

None of the aforementioned variables assumed statistical significance between the two subgroups. Results, however, show that as a whole, 11 out of the 12 patients had at least one indicator of high estrogen. Our results point in the direction that elevated estrogen is probably associated with MBC. Further meta-analysis of similar studies can be helpful to explain the dynamics of this association. Our statistical analysis was limited due to the small sample size, which is due to the extreme rarity of the disease.