Cancer, Male Breast Cancer


Article Author:
Ahmed Khattab


Article Editor:
Dulabh Monga


Editors In Chief:
Jesse Cole


Managing Editors:
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Frank Smeeks
Kristina Soman-Faulkner
Benjamin Eovaldi
Radia Jamil
Sobhan Daneshfar
Saad Nazir
William Gossman
Pritesh Sheth
Hassam Zulfiqar
Navid Mahabadi
Steve Bhimji
John Shell
Matthew Varacallo
Ahmad Malik
Mark Pellegrini
James Hughes
Beata Beatty
Hajira Basit
Phillip Hynes


Updated:
2/14/2019 8:39:41 AM

Introduction

Although breast cancer is typically synonymous as a disease which commonly occurs in women, it does occur in men as well. This is because although minimal in quantity, men do have breast tissue that has the potential to become malignant similarly to women, albeit much less commonly. While male breast cancer (MBC) is rare, only occurring in 1% of all breast cancers [1], it does occur, and it is important to be cognizant of its reality and potential.

Etiology

When discussing the etiology of male breast cancer, one must uncover the potential genetic or environmental risk factors. It is also important to be mindful that the majority of males diagnosed with MBC have no identifiable risk other than increasing age (average age of diagnosis of 71 years).[2]

Similarly to women, males have a higher risk of breast cancer if they have a first- or second-degree relative with breast cancer. Studies have shown that an affected sibling or parent of either gender may increase the risk of breast cancer in either the males or females in the family. Bevier et al. (2012) noted in their study that the relative risk (RR) of breast cancer was similar in either offspring when the father or mother was affected (RR = 1.73 and 1.74, respectively), but the risk was slightly higher in the females when the brother is affected as opposed to when the sister is affected (RR = 2.48 and 1.39, respectively).[3] Also, in addition to a family history of breast cancer, males with a BRCA mutation appear to have increased risk for breast cancer as well. Although rare for a male to have a BRCA mutation, those with BRCA2 carrier mutation have a 6% increased risk and BRCA1 with a 4% risk of developing the disease.[4] Other genetic disorders have been implicated in increasing the risk of MBC including Klinefelter syndrome (47, XXY), Cowden syndrome (PTEN tumor suppressor gene), Li-Fraumeni syndrome (TP53), Lynch syndrome (PALB2 and mismatch repair genes)[2],[4],[2]

The alterations in estrogen to androgen ratios is important to note when discussing the etiology of male breast cancer. Estrogen, which stimulates ductal development in breasts, has also been implicated as a potential risk factor for MBC similarly to women. Klinefelter syndrome, as previously mentioned, may increase the risk of MBC through excess estrogen stimulation. Other potential triggers have also been identified and include obesity, marijuana use, hepatic dysfunction, thyroid disease, and estrogen-containing medications.[2] Likewise, a decrease in circulating androgens would result in elevations of the estrogen ratios, and this may occur from conditions such as cryptorchidism, orchitis, and orchiectomy.[5]

Lastly, environmental factors have also been implicated in the possibility of increasing the risk of male breast cancer. As with women, previous radiation therapy has been noted as a potential risk factor. Of note, radiotherapy has been used to treat gynecomastia, but these patients have been found to have a 7-fold increase in the risk of MBC.[6] In addition, certain occupations have been found to increase the risk of MBC including steel and rolling mills as well as occupations involved with organic solvents such as trichloroethylene.[7]

Epidemiology

Male breast cancer is a relatively rare malignancy when compared to female breast cancer (FBC) with a known ratio of 1 male case to 100 in females and occurs in about 1% of all breast cancers.[8] Regarding male cancers in general, it accounts for 0.5% of all cancer diagnosis in men, but there has been a recent concern about the rising incidence in the past few decades.[8] Studies have hypothesized that in addition to obesity and alcohol, dietary factors may be exacerbating the incidence of MBC, but concrete research and evidence regarding specific dietary patterns have yet to be established.[9] Despite these plausible associations, many individuals who are diagnosed with male breast cancer have no identifiable risk factors.[8]

Histopathology

The most common type of breast cancer seen in men is invasive ductal carcinoma, which constitutes approximately 90% of all male breast cancer.[10] Other types implicated are medullary, papilloma, and lobular. Ductal carcinoma in situ is not commonly found due to lack of awareness and stigmas related to MBC. This then leads to delayed diagnosis and poorer outcomes of the patients.

In regards to hormone expression in male breast cancer, approximately 90% express the estrogen receptor (ER), and 81% express the progesterone receptor.[10] Studies have also found that expression of these hormone receptors is more prevalent than FBC.[11] Thus, adjuvant therapy is usually predicated on inhibition of these receptors which is discussed further in the treatment and management section.

History and Physical

Male patients commonly present to the clinic complaining of a painless mass in a unilateral breast. Other potential symptoms include nipple retraction, nipple discharge, ulceration, and pain.[2] Masses in males are typically easier to appreciate than in females due to the smaller breast size, although gynecomastia may mask the condition. Also, when discussing the history of presenting illness, it is vital to discuss the potential family history of breast cancer, patient’s past medical history, occupation, and whether there has been previous estrogen or radiation exposure.

Evaluation

Similar to breast cancer in women, the diagnosis of MBC is made by a triple assessment which includes clinical assessment, mammography, or ultrasonography, and core biopsy.[10] Mammography is an effective diagnostic method with a sensitivity of 92% and a specificity of 90%; although due to size and volume differences in male breasts, this modality may be limited at times. Given this, ultrasound-guided core biopsy gives the most definitive diagnosis of MBC and is preferred over fine needle aspirations.[10]

Treatment / Management

Treatment and management of male breast cancer typically follow the same rationale of breast cancer in females, which consists of resection followed by adjuvant endocrine therapy, chemotherapy (CT), or radiotherapy.[12] Management is guided by prognostic factors and is further discussed in the oncology section.

Differential Diagnosis

Common differentials a clinician should be mindful of during the evaluation of male breast cancer are gynecomastia, abscess, lipoma, metastatic disease, and sarcomas, although these are much rarer.[2]

Surgical Oncology

For early-stage disease (T1-T2, N0-N1), simple or modified radical mastectomies that do not involve the additional removal of the pectoralis muscle have been found to be the preferred choice of resection because retrospective studies have not shown a mortality or reoccurrence benefit with radical approaches of resections.[13] Axillary or sentinel lymph node biopsies are typically obtained as well to designate prognostic factors further. Furthermore, due to the relatively small volume of breast tissue in men, breast-conserving approaches are rarely entertained.

Radiation Oncology

The rationale and indications for radiotherapy in MBC are similar to those with FBC which include if the patient underwent breast-conservative resections as well as those with advanced disease (T3 or T4) who underwent a radical mastectomy.[13] Despite these indications, the data regarding the mortality benefit of radiotherapy for MBC is less clear.[2]

Medical Oncology

As described above, breast cancer in males more commonly expresses ER, and thus, endocrine therapy is a vital part of management. Tamoxifen is the common choice of treatment although aromatase inhibitors have been identified as a potential therapy; however, its role as isolated adjuvant therapy is limited.[12] The data is also limited concerning the efficacy of adjuvant CT. Retrospective studies have shown hormonal therapy to be more efficacious for breast cancer in males than CT[2] for advanced disease. Due to the limitations of data, the indications of CT in male breast cancer have been taken from female breast cancer indications and include positive lymph nodes with tumor size greater than 1 cm and negative hormone receptors. Given these indications, oncologists typically select for hormonal therapy first, and in the event of failure of this treatment modality, do they consider the role of CT.[12]

Staging

The staging workup regarding male breast cancer is classified similarly to breast cancer in females and consists of the tumor, node, and metastasis (TMN) staging system. Unfortunately, due to common delayed diagnosis of male breast cancer, approximately 40% of all male breast cancer at the initial diagnosis is found to be stage III or IV disease.[2]

Prognosis

Due to delayed diagnosis commonly found in male breast cancer, the overall 5-year survival is approximately 40% to 65%. When stratified, stage I is 75% to 100%, stage II is 50% to 80%, stage III is 30% to 60%, and stage IV is 20% to 30%.[10] Despite these findings, when matched with various prognostic factors such as age, stage of disease, and grade, the mortality of males with breast cancer has not been found to be significantly greater than in females with breast cancer.[10]

Deterrence and Patient Education

Routine screening of males with breast cancer is not established due to the rarity of occurrence. Yet, males (especially those older than 35) should be educated on the potential risk factors discussed and be advised on genetic counseling if they have a family history of breast cancer (in both males and females) or other cancers that may be triggered by a BRCA gene, for example, ovarian, pancreatic, testicular, or prostate cancers.[14]

Enhancing Healthcare Team Outcomes

the management of breast male cancer is with a multidisciplinary team that consists of an oncologist, surgeon, radiation therapist, dietitian and mental health counselor. The majority of these patients initially present to their primary care provider or nurse practitioner. Unlike females, there may not be any risk factors and hence any mass should be worked up and a malignancy ruled out.

An aspect of male breast cancer that is frequently overlooked is the negative stigmas that these patients routinely face which leads them to feel quite isolated and vulnerable. Psychosocial support through various interdisciplinary teams should be offered to allow for a more normalization of their condition and experience as well as to create an atmosphere of nonjudgmental dialogue to address their concerns and potential stigmas. Stage for stage the prognosis for male breast cancer is the same as in females.[15] (Level V)


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Cancer, Male Breast Cancer - Questions

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Where is carcinoma of the male breast is usually found?



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A 60-year-old man undergoing hormonal therapy for prostate cancer presents with a painless palpable retroareolar mass. Mammogram shows spiculated mass. Which of the following should be included in the report comments?



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Which of the following gene mutations has been implicated as a potential trigger of human mammary oncogenesis leading to male breast cancer?



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A 34-year-old male presents to the clinic reporting his sister was recently diagnosed with breast cancer at 36 years of age. He is curious if he has an increased risk of breast cancer given his sister's recent diagnosis. How would you address his concern?



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Cancer, Male Breast Cancer - References

References

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Fentiman I, Male breast cancer: a review. Ecancermedicalscience. 2009     [PubMed]
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Massarweh SA,Sledge GW,Miller DP,McCullough D,Petkov VI,Shak S, Molecular Characterization and Mortality From Breast Cancer in Men. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2018 May 10     [PubMed]
Niewoehner CB,Schorer AE, Gynaecomastia and breast cancer in men. BMJ (Clinical research ed.). 2008 Mar 29     [PubMed]
Sasco AJ,Lowenfels AB,Pasker-de Jong P, Review article: epidemiology of male breast cancer. A meta-analysis of published case-control studies and discussion of selected aetiological factors. International journal of cancer. 1993 Feb 20     [PubMed]
Cocco P,Figgs L,Dosemeci M,Hayes R,Linet MS,Hsing AW, Case-control study of occupational exposures and male breast cancer. Occupational and environmental medicine. 1998 Sep     [PubMed]
Ferzoco RM,Ruddy KJ, The Epidemiology of Male Breast Cancer. Current oncology reports. 2016 Jan     [PubMed]
Kreiter E,Richardson A,Potter J,Yasui Y, Breast cancer: trends in international incidence in men and women. British journal of cancer. 2014 Apr 2     [PubMed]
Rudlowski C, Male Breast Cancer. Breast care (Basel, Switzerland). 2008     [PubMed]
Shandiz FH,Tavassoli A,Sharifi N,Khales SA,Kadkhodayan S,Khales SA, Hormone receptor expression and clinicopathologic features in male and female breast cancer. Asian Pacific journal of cancer prevention : APJCP. 2015     [PubMed]
Yalaza M,İnan A,Bozer M, Male Breast Cancer. The journal of breast health. 2016 Jan     [PubMed]
Cutuli B,Lacroze M,Dilhuydy JM,Velten M,De Lafontan B,Marchal C,Resbeut M,Graic Y,Campana F,Moncho-Bernier V, Male breast cancer: results of the treatments and prognostic factors in 397 cases. European journal of cancer (Oxford, England : 1990). 1995 Nov     [PubMed]
Cavanagh H,Rogers KM, The role of BRCA1 and BRCA2 mutations in prostate, pancreatic and stomach cancers. Hereditary cancer in clinical practice. 2015     [PubMed]
Nemchek L, Male Breast Cancer: Examining Gender Disparity in Diagnosis and Treatment. Clinical journal of oncology nursing. 2018 Oct 1;     [PubMed]

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