A Clinico-pathological Study of Male in Yazd, Iran (1992-2007)

1 Ali Akbar SALARI, 2 Shokouh TAGHIPOOR, 3 Hassan AMIR 1 Department of Surgery, 2 Department of , Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran, 3 Department of Clinical Anatomy, American University of Antigua, College of Medicine, St. Johns, Antigua and Barbuda.

ABSTRACT INTRODUCTION

Male (MBC) is an uncommon condition. It Male breast cancer (MBC) is an uncommon condition. It accounts for less then 1% of all breast and even fewer accounts for less then 1% of all breast cancers and even of all malignancies occurring in men. Between 1992 and 2007, fewer of all malignancies occurring in men.1 MBC presents a total of 6673 cancer cases were registered in the pathology commonly as a lump and at times is associated with department of Shahid Sadoughi University of Medical Sciences ulceration or even a fungating mass.2 and Health Services, Yazd, Iran. Of these 3740 patients (56.46%) were males. Eight of these cases (0.21 %) had breast However, MBC is reported in greater numbers from cancer. The overall male female ratio for MBC was 0.017:1. counties south of Sahara.2, 3 Such a finding has also been The mean age of our patients was 63.62 years (SD = 11.63). reported amongst the African American population also.3, Stage III and IV disease was observed in 87.5 percent of our 4, 5 Recently, one study reported that male female ratio patients. Histological analysis revealed that 87.5% of patients was narrow in those populations where cervical cancer had infiltrating ductal carcinoma. Hormone receptor status of was registered as a leading cancer.3 Cancer registry data the tumor was positive in 87.5 percent of patient for from Iran indicates MBC is rare.6, 7, 8 However, review of and receptor respectively. These observations are literature revealed that no report is available from Iran discussed for the need for early detection of MBC and national that describes the clinico-pathological profile of MBC consensus for an evidence based management of MBC in Iran. patients.9

Address for Correspondence: Prof. H. Amir, P.O. Box W-1451, Department of Clinical Anatomy, American University of Antigua, College of Medicine, St. Johns, Antigua and Barbuda 165 E mail: [email protected], Tel: (268) 481 8881. Hassan Amir

This study presents clinico-pathological profile and stage for Disease Control and Prevention (CDC), Atlanta, of MBC at presentation for 8 patients diagnosed at our Georgia and the results are presented commensurate with centre during 1992 to 2007 period. The observations are a descriptive study. discussed for the need for early detection of MBC and a national consensus for an evidence based management of RESULTS MBC in Iran. During the study period a total of 6673 cancer cases were PATIENTS AND METHODS registered. Of these 3740 patients (56.46%) were males. Eight of these cases (0.21 %) had breast cancer. The overall Between April 1, 1992 and March 31, 2007, 8 consecutive male female ratio for breast cancer was 0.017:1. Table 1. patients with histological proven male breast cancer (MBC) were identified using the cancer data registered in the Seventy five percent of patients with MBC were in 60-79 pathology department of Shahid Sadoughi University of years agegroup (46-76 years). The mean age was 63.62 Medical Sciences and Health Services, Yazd, Iran. We years (SD = 11.63) and the median age was 67.0 years. describe the demographics and clinical characteristics of Except for 1 case 87.5 percent of patients in this study had these 8 MBC patients and discuss the implications of our late disease (stage III and IV). Three patients (37.5%) had findings relative to analogous centers and the care for such metastatic lung disease. The tumor occurred more patients in different geographical regions. frequently in the right breast (62.5%). Infiltrating ductal carcinoma was reported in 87.5 percent of patients studied. For each patient studied data was extracted from patient’s was seen in only one patient with stage case records that included age of patient, affected breast, I disease. Hormone receptor status of the tumor was positive tumor size, skin involvement (fixation, ulceration), fixation for estrogen (7 patients) and progesterone receptor (7 of tumor to chestwall, lymph node status, histopathological patients) Table 2. report of the tumor, hormone receptor status of the tumor and treatment offered. Post treatment follow-up data was Different combinations of treatment that was offered to also collected. These findings were recorded using a our patients are listed in Table 3. standardized data collection forms. Metastatic status was determined by X-rays of the chest, abdominal ultrasound Stage of disease at presentation, treatment offered and and CT scanning. follow-up period of each patient is shown in Table 4. One patient with Stage I disease was followed for 60 months The Tumor, Nodes and Metastasis (TNM) classification of with an uneventful post-operative period. Four patients the International Union Contra Cancer (UICC) was used had stage III disease. Of these 4 cases one died after 9 for staging breast cancer in our patients. This method months, 1 was lost to follow-up after 13-24 months and 2 describes the disease in terms of the tumor size (T1, 2, 3, 4), patients did not attend the clinic after 48 months. Stage IV nodal involvement (N1, 2, 3), and distant metastasis (M1). disease was seen in 3 cases, All patients had metastatis to the lung. Two of these cases died within 6-9 months after The data were processed and analyzed using the Epi Info, treatment while one patient died between 10-12months. version 3.3.2, 2005, statistical program developed by Centre The last case did not receive adjuvant therapy.

Table 1. Sex specific prevalence of breast cancer in Yazd, Iran 1992-2007

Study Total Male Male Breast Total Female Female Breast M:F Ratio Period Cancer (N) Cancer (N) Cancer (N) Cancer (N)

1992-1997 956 3 791 125 0.024:1

1997-2002 1376 1 1101 180 0.005:1

2002-2007 1408 4 1041 141 0.028:1

Total 3740 8 2933 446 0.017:1

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Table 2. Demographics and clinical characteristics of male breast cancer patients in Yazd, Iran 1992-2007

Patients characteristic N % Patients characteristic N %

Age (years) Positive lymph nodes (N) 40 - 49 2 25.0 0 1 12.5 50 - 59 0 0 1 1 12.5 60 - 69 3 37.5 2-5 6 75.0 70 - 79 3 37.5 Metastatic Disease (M) 3 (Lung) 37.5 Year of diagnosis Skin involvement 6 75.0 1992 - 1996 3 37.5 1997 - 2002 1 12.5 Breast side affected 2003 - 2007 4 50.0 Right 5 62.5 Left 3 37.5 Stage of disease (TNM) I 1 12.5 Hormone receptor status IIIA 2 25.0 ER positive 7 87.5 IIIB 2 25.0 PR positive 7 87.5 IV 3 37.5

Tumor size (cms.) (T) Histopathological analysis > 2 3 37.5 Infiltrating ductal ca 7 87.5 > 5 5 62.5 Comedocarcinoma 1 12.5

Table 3. Treatment given to male breast cancer patients in Yazd, Iran 1992 - 2007

Surgery N (%)

Radical mastectomy 4 (50)

Mastectomy with node dissection 3 (37.5)

Mastectomy 1 (12.5)

Adjuvant systemic therapy

Chemotherapy + radiotherapy + 4 (50)

Chemotherapy + radiotherapy 1 (12.5)

Chemotherapy 1 (12.5)

Tamoxifen 1 (12.5)

No therapy 1 (12.5)

Austral - Asian Journal of Cancer ISSN-0972-2556, Vol. 7, No.3, July 2008 pp 165-169 167 Hassan Amir

Table 4. Post treatment follow-up of male breast cancer patients in Yazd, Iran. (1992-2007)

Patient and Year Stage of Treatment Follow-up period of Diagnosis disease(TNM) Given (months)

6-9 10-12 13-24 25-48 49-60

Patient 1 (1992) Stage IIIa RM+C+R+T alive died - - -

Patient 2 (1993) Stage IIIb RM+C+R+Talive lost to follow-up

Patient 3 (1995) Stage IV RM+C+R died - - - -

Patient 4 (1998) Stage IV RM alive died - - -

Patient 5 (2003) Stage I M+T Alive

Patient 6 (2005) Stage IIIa M+LNR+ C+R+Talive lost to follow-up

Patient 7 (2006) Stage IIIb M+LNR+ C+R+T alive lost to follow-up

Patient 8 (2007) Stage IV M+LNR+C died - - - -

RM=, M=Mastectomy, LNR=Lymph node resection, C=Chemotherapy, R= Radiotherapy, T=Tamoxifen

DISCUSSION breast cancer in those populations where cervical cancer was in leading position. In Iran men live longer and cervical This is the first study from Iran reporting on male breast cancer is uncommon.6, 7, 8 Possibly, this would explain the cancer. Of all the male cancers studied 0.21percent were rarity of MBC in Iran. patients with breast cancer. Table 1. Though this condition is rare, recently the incidence of MBC is on the rise in The majority of our patients had stage III and IV disease USA.10 However, in sub Saharan Africa MBC cases have (87.5 percent) (Table 2). Late disease is not an unusual decreased after the advent of HIV/AIDS epidemic in presentation of male breast cancer.2, 10, 11, 15 The rarity of 1983.11 An increase in longevity in the US population may this cancer and the low index of suspicion of both patients explain the increase in cases as age is a major risk factor for and their treating physicians have been largely responsible most solid tumors.12 Conversely, MBC incidence has for delay in diagnosis.15 decreased significantly in countries south of the Sahara. This decline has been attributed to HIV/AIDS associated Predominately, histological type of the disease in this study mortality. This explanation becomes even more compelling was invasive ductal carcinoma in 87.5 percent2, 15 Table 2. because these changes were observed after the advent of HIV/AIDS in 1983.11 Estrogen and progesterone receptor positively was 87.5 percent in each group in this study Table 2. Different MBC’s annual incidence increases after 35 years of age, combinations of treatment were offered to our patients. 0.1 cases per 100,000 men, to 11.1 cases at the age >85 This included surgery, chemotherapy, radiotherapy, years.13 The median age of our patients was 67.0 years. tamoxifen or a combination of these treatments Table 3. It The average life expectancy in Iran for men is 76.3 years.14 has been reported that men with breast carcinoma do Despite the long life that people live in Iran yet there were benefit with systemic therapy but the greatest benefit is only 8 cases over 15 years. This would suggest that a achieved by hormonal therapy.15, 16 Though different combination of advance age and unidentified factor may modalities of treatment are offered to patients with MBC be responsible for the pathogenesis of MBC. In one study3 evaluation of the outcome becomes difficult due to its rarity. it has been suggested that the M:F ratio was narrow for In our study one patient with early disease (stage I) was

Austral - Asian Journal of Cancer ISSN-0972-2556, Vol. 7, No.3, July 2008 pp 165-169 168 Male Breast Cancer in Iran offered mastectomy and tamoxifen and had an uneventful 5. Muir, C., Waterhouse, J., Mack, T., Powell, J. and Whelan, S. post treatment period till 60 months of follow up. Cancer incidence in five continents. IRAC scientific publication No.88. London: Oxford University Press, 1987. 6. Sadjadi A, Malekzadeh R, Derakhshan MH, Sepehr A, Nouraie The follow up of patients ranged from 6 to 60 months in M, Sotoudeh M, Yazdanbod A, Shokoohi B, Mashayekhi A, this study Table 4. During this period there was a progressive Arshi S, Majidpour A, Babaei M, Mosavi A, Mohagheghi MA, reduction of patients attending follow-up clinic. Alimohammadian M. Cancer occurrence in Ardabil: results of a population-based cancer registry from Iran. Int J Cancer A total of 87.5 percent of our patients were in late stage 2003; 107: 113-18 disease (stage III and IV). Due to paucity of records 7. Babaei M, Mousavi S, Malek M, Tosi G, Masoumeh Z, Danaei mortality data was not available. High mortality is associated N, Gafar G. Cancer occurrence in Semnan Province, Iran: with late stage disease.15 Possibly, these deaths may explain results of a population-based cancer registry. Asian Pac J Cancer Prev 2005; 6:159-64 the declining visits at the follow-up clinic. 8. Hossein Somi M, Mirinezhad K, Farhang S, Jazayeri E, Sani A, Seif-Farshadi M, Golzari M, Kashef S, Sadegy M. The early detection of MBC and its treatment should be Gastrointestinal cancer occurrence in East Azarbaijan: a five the major components of a strategy aimed at improving year study from North Western Iran. Asian Pac J Cancer Prev 2006; 7: 309-12 therapeutic outcome. To achieve this goal we must 9. PubMed (home page on Internet) National Library of Medicine formulate a combined national policy for the and National Institute of Health, Bethesda, Available from: management of MBC in Iran that includes ensuring the www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed collection of quality clinical data and adopting a standard 10. Giordano SH, Cohen DS, Buzdar AU, Perkins G, Hortobagyi GN. Breast carcinoma in men. A population-based study. Cancer staging system (UICC / TNM staging classification). This 2004; 101: 51–57. would enable comparison of outcome with different 11. Amir H, Kaaya EE, Kwesigabo G, Kiitinya JN. Breast cancer research centers. It is also pertinent that an internationally before and during the AIDS epidemic in women and men: a accepted evidence-based standard of care for MBC study of Tanzanian Cancer Registry Data 1968 to 1996. J Natl Med Assoc 2000; 92:301-5. patients be adopted. 12. Fentiman IS, Tirelli U, Monfardini S, Schneider M, Festen J, Cognetti F, Aapro MS. Cancer in the elderly: why so badly REFERENCES treated? Lancet 1990; 335:1020-22. 13. Gennari R, Curigliano G, Jereczek-Fossa BA, Zurrida S, Renne G, Intra M, Galimberti V, Luini A, Orecchia R, Viale G, 1. Giordano SH, Buzdar AU, Hortobagyi GN. Breast cancer in Goldhrisch A, Veronesi U. Male breast cancer: a special men. Ann Intern Med. 2002: 137:678-87. therapeutic problem. Anything new? Int J Oncol 2004; 24:663- 2. Amir H, Hirji KF. Carcinoma of the male breast in Tanzania. J 70. Natl Med Assoc 1992; 84:337-40 14. Statistics Division, United Nations, New York, NY 10017, USA., 3. Amir H, Makwaya CK, Moshiro C, Kwesigabo G. Carcinoma of 2008 http://unstats.un.org/unsd/contactus.htm the male breast: a sexually transmitted disease? East Afr Med 15. Fentiman IS, Fourquet A, Hortobagyi GN. Male breast cancer. J 1996: 73:187-90. Lancet. 2006; 367:595-604. 4. Anderson WF, Althuis MD, Brinton LA, Devesa SS. Is male 16. Giordano SH, Perkins GH, Broglio K, Garcia SG, Middleton breast cancer similar or different than female breast cancer? LP, Buzdar AU, Hortobagyi GN. Adjuvant systemic therapy for Breast Cancer Res Treat 2004; 83:77-86. male breast carcinoma. Cancer. 2005; 104:2359-64.

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