A Descriptive Study on Male Breast Cancer and Its Contingency in Pakistan

Introduction Cancer is one of the most researched topics of the age. Since last twenty years, a number of considerable advancements have been done in discernment of breast cancer so that it can be pronounced at initial stages which will ultimately lead to better management [1]. According to GLOBCAN cancer stats of 2018, breast cancer is the second most rampant cancer and is one of the top 10 most prevalent cancers [2].


Introduction
Cancer is one of the most researched topics of the age. Since last twenty years, a number of considerable advancements have been done in discernment of breast cancer so that it can be pronounced at initial stages which will ultimately lead to better management [1]. According to GLOBCAN cancer stats of 2018, breast cancer is the second most rampant cancer and is one of the top 10 most prevalent cancers [2]. Breast cancer in males is a scanty as compared to females [3]. Out of all the breast cancer registrations, registration for male breast cancer ranges from 0.6%-01%. The reason for these minimal numbers of registrations is lack of awareness and abstruse concept of MBC in the society. The breast tissue mass is comparatively low in males as compared to females and distinction in hormonal medium leads to low pervasiveness of MBC [4]. The SEER (Surveillance, Epidemiology, and End Results) reported during 1973-2000 that breast cancer was most prevalent in the age group 52-71 ( Figure 1).
Occurrence of breast cancer in both male and female have increased by 20% since the last 2 decades. The global occurrence of male breast cancer has been approximately increased from 1 to 1.5 per 100,000 men. The rate of male breast cancer has become 1 in 1000 males in USA [5]. This pervasiveness is much higher in central African and Asian countries [6]. In Pakistan the frequency of MBC is recorded as 2 men per every 100 females [7]. The frequency of MBC depends widely upon the geographical distribution and ethnicity of individuals [8,9]. Approximately, 2500 cases of breast cancer are reported in men in the year 2017 [10].
Individuals with a positive family history are more likely to develop MBC or non-breast tumors by 15-20% [11]. Gynecomastia (enlargement of male breast should not be confused with MBC, both of the diseases are based on distinct concepts whereas it may be found in patients with MBC [12,13]. Genetics play an important role in MBC susceptibility [14]. Genetic mutations in BRCA1 and BRCA2 increase the likelihood of MBC [15]. BRCA2 mutations are more frequently detected [16].
Several other factors that facilitate the onset of MBC are klinefelter syndrome, hepatic manifestations and diseases of male genitals i.e. prostate cancer, cryptorchidism etc, these disorders are found complementary to male breast cancer [17,18]. Symptoms and signs of MBC are seen in juvenile ages in individuals with klinefelter syndrome. Klinefelter syndrome increases the probability of male breast cancer by 50% [19].
CHEK2 and PALB2 germline mutation also increase the plausibility of MBC [20,21]. The identification of MBC is done by either mammography or ultrasound, therefore the clinicalpathological layout of MBC diverges with the female layout [22,23] but biopsy, genetic testing, histological analysis and biomarker identification are more explicit and reliable methods for the detection of MBC.
The characteristics of MBC mimic the characteristics of postmenopausal females [24,25]. MBC is substantially hormone (estrogen) receptor positive and her-2/neu negative, MBC predominantly consist of ductal carcinomas and rarely develop lobular carcinoma whereas lobular carcinomas are more widespread in females with breast cancer [26] in MBC BRCA2 mutations are often overly expressed in contrast to BRCA1 mutations [27]. The survival rates have drastically increased in the last couple of decades [29] with the latest advancements in the field of genetic testing. Multiple genes that are associated with cancer are identified and discovered by using NGS (next generation sequencing) at fairly low cost, these genes (CDH1, PTEN, STK11, TP53 and mismatch genes hMLH1, hMLH2) are available for genetic testing (93).

Symptoms and Signs
The symptoms and signs of the male breast cancer appear at a much-delayed stage. As considering the anatomy of male breast cancer it should be easily diagnosed but it's not. The reason is that MBC becomes symptomatic at advanced stages and also not enough information or research is available (73). Painful or painless lumps, Dimpling breast ,Puckering over skin of the breast, Change in size, Rash or redness on the area around breast ,Nipple discharge ,Redness over nipples or bleeding ,Nipple retraction; seeing any of these potential features and moreover if these symptoms persist one should immediately consult a doctor without a further delayed.

Staging of Male Breast Cancer
The staging of the breast cancer in male is no more different than female, the method adopted for evaluation are the same. Size

Diagnosis and Screening
The steps followed by the diagnosis of MBC are listed below, starting from the primary to advanced diagnostic techniques,

Her-2 Test:
It is a test that is used to check the amount of her-

Her-2 enriched
This type of cancer shows high levels of her-2/neu protein and is mostly found in women and is very rare in males.

Advanced Methods in Staging
Once the presence of cancer is confirmed furthermore tests such as chest scans and bone scans are run to check the extent of the tumor and for better staging of the disease.

Treatment of Male Breast Cancer
Surgical incision is the main first line treatment for the male breast cancer the approach is similar in both the genders. tumors.AI therapy (Aromatase inhibitor therapy) is also employed in adjuvant endocrine therapy but its scope is limited therefore Tamoxifen therapy is preferred over AI therapy [31,32].

Prognostic Factors
Although these are the available treatments, but every patient behaves differently to these therapies this is because of the variable

Background
Herein we discuss a case reported in a local hospital of Pakistan. This was a rare case which reported recently. A 50-yearold man reported the presence of a lump in his breast. After further examinations the therapies were recommended. The patient had a hard lump in the breast for almost three years when the subject was brought under consideration following test were run for the discernment of the lump that either it be cancerous or not.

Testing
Some tests were run to confirm that either the lump is cancerous or not.
Cytology Test: It confirmed the suspiciousness of the lump. At that time the lump was hard was about the size of 6x5 cm hard. It was diagnosing to be a class three smear which is highly suspicious.
The cytological reports confirmed it to be unusual, but it was most likely to begin.

Treatment
The patient went into MRM of the right breast. After that he went into radiotherapy. The patient secured 2 cycles of SSD therapy with 100cm in both fields on a daily dose of 220. After that the patient went for further evaluation which is unknown to us.

Discussion
The reason for discussing this case is to discuss and compare the therapeutic follow-up that is commonly adopted in Pakistan for the management of male breast cancer. Therefore, the methods that are opted for the diagnosis and management of male breast cancer are ideal [33,34]. As per the international standards the first and foremost method of identification is physical examination which is followed by clinical testing, both these methods are well employed and well utilized Furthermore, the treatment strategies opted was also according to the marked standards. Lumpectomy was then followed by SSD radiation cycles after that the patient was reassessed for the recurrence of any kind of cancerous mass Despite of all these factors Pakistan is still unable to provide novel identification techniques so that's why breast cancer in both males and females is not identified at initial stages Moreover, Pakistan lacks established treatment protocols and genetic testing, even if these settlements are available they are not as widespread as they should be. Therefore, the survival rate is a bit lower in Pakistan just because of these few reasons [35,36].
Another factor that is the most prevalent cause for the poor prognosis of such patients is the financial limitation, Pakistan is a developing country therefore it is very difficult for people to afford such costly treatments and medication. Commonly employed medicine for male breast cancer trastuzumab is mostly cut down by the doctors because it's out of the financial range of the patients The main reason to discuss such unusual cases is that Pakistan should establish its own databases that cover all the male breast cancer cases occurring in the country also it should be widely accessible for everyone so it might raise awareness among people that breast cancer is not only confined to the female body but it can also spread to males as well [37,38].

Future Prospective
The future perspectives for the treatment of male breast cancer or breast cancer in general are a novel therapy that is characterized as microRNA therapy. MicroRNA has been widely studied for its role in the identification of several types of cancer but its unique property of gene silencing is overall.

Microrna Therapy
The microRNA therapy can be applied but not enough studies are there to support it. secondly there are a number of barriers that hinder the use of miRNA therapy, the barriers are listed below

Nanoparticles
Nanoparticles are a new and completely novel concept. It has attracted researchers' attention because of their robustness.
Nanoparticles exhibit versatile characteristics they have multiple uses and can be employed for different medicinal purposes. There are several uses for the application of nanoparticles 1.
They are excellent vectors for drug delivery.

2.
They are used for the identification of cancer at initial