Topic: Prevalence of genetically acquired Breast Cancer in the Abbottabad region.

Incharge: Ms Asma Khan

Ms Rabia

Authors: Areeba, Ajwa Munir, Ajwa Inshaal, 

Emaan, Amna, Amina Ali Khan, Dua Rehman

ABSTRACT:

Breast cancer is the most common malignancy in women in the world and second leading cause of cancer-related death. However, in patients with a suggestive personal and/or family history, a specific predisposing gene is identified in some cases. In this study we looked for genes associated with breast cancer and how these inherited genes can play part in breast cancer development. For this purpose 168 Breast cancer patient’s data was retrieved and after going through their recorded history and biopsy reports. We found out that only 8 patients had genetic mutations. 3 out of 8 had reportedly BRCA-1 mutations. 5 out of 8 had BRCA-2 gene mutation. these findings show that  the probability of genetically inheriting the mutated gene is still 2-4% which is approximately close to the probability shown by other researchers i.e., 5-7 percent which was observed during our literature review. This study can lead to the innovation in breast cancer therapy by targeting mutated genes and can help to prevent the incidence of breast cancer.

INTRODUCTION:

Cancer is a disease in which some of body cell grow uncontrollably and spread to other parts of body. Cancer can start almost anywhere in human body which is made up of trillions of cell. Normally human cells grow and multiply to form new cells as body needs them when cells grow old and become damaged they die and new cells take their place. Some times, this process break down and abnormal cells grow and they form tumors and different type of cancer. When abnormal lungs cell grow it causes lung cancer. Similarly when abnormal breast cell grow out of control it form tumor it is called breast cancer.

Breast cancer is  abnormal  breast cell growth that form tumor. Breast cancer is most prevalent type of cancer in world. Breast cancer is a disease in which certain cells in the breast become abnormal and multiply uncontrollably to form a tumor. Throughout world Cancer poses major health risk for women. Every year one million women diagnosed with breast cancer worldwide. One of the first signs of breast cancer is usually a lump in the breast or underarm. The lump may be painless at first, but it can grow and become painful. Another symptom to look out for is changes in the shape or texture of your breast. This can include dimpling, puckering, redness, or thinning of the skin on the breast. Breast cancer can also cause pain in the breast that doesn’t go away.

There are a variety of factors that affect your breast cancer risk. Some you can’t change, such as being a woman, growing older, and inheriting a gene mutation linked to breast cancer. But you can change other risk factors such as being overweight, not exercising regularly, smoking cigarettes, drinking alcohol, or eating unhealthy food  by making healthier lifestyle choices.  You have a higher risk of developing breast cancer if you have close relatives who've been diagnosed with the disease, particularly first-degree relatives, such as your sisters, mother, or daughters. Your risk increases if you have multiple close relatives who have had breast cancer, and if a first-degree male relative (your brother or father) has been diagnosed with breast cancer. In some cases, a strong family history of breast cancer is linked to having an abnormal gene associated with a high risk of breast cancer, such as the BRCA1 or BRCA2 gene.

A hereditary predisposition to breast cancer significantly influences screening and follow-up recommendations for high-risk women. However, in patients with a suggestive personal and/or family history, a specific predisposing gene is identified in <30% of cases.  Up to 25% of hereditary cases are due to a mutation in one of the few identified rare, but highly penetrant genes (BRCA1, BRCA2, PTEN, TP53, CDH1, and STK11), which confer up to an 80% lifetime risk of breast cancer.  There is no single definition of ‘familial’ breast cancer, but generally accepted criteria include: 1) At least three breast and/or ovarian cancer cases in a family. 2) Two breast cancer cases in close relatives, with at least case diagnosed before age 50. 3)Two breast cancer cases in a family diagnosed before 40 years of age. 4) Any male breast cancer with a family history of ovarian cancer or early onset female breast cancer. 5) Breast  and ovarian cancer in the same patient.

Cancers occur when a buildup of mutations in critical genes, those that control cell growth and division or repair damaged DNA, allow cells to grow and divide uncontrollably to form tumors. In most cases of breast cancer, these genetic changes are acquired during a person's lifetime and are present only in certain cells in the breast. These changes, which are called somatic mutations, are not inherited. Somatic mutations in many different genes have been found in breast cancer cells. Less commonly, gene mutations present in essentially all of the body's cells increase the risk of developing breast cancer. These genetic changes, which are classified as germ-line mutations, are usually inherited from a parent. In people with germ-line mutations, changes in other genes, together with environmental and lifestyle factors, also influence whether a person will develop breast cancer.

 

 Some breast cancers that cluster in families are associated with inherited mutations in particular genes, such as BRCA1 or BRCA2. These genes are described as "high penetrance" because they are associated with a high risk of developing breast cancer and ovarian cancer and a moderate risk of developing pancreatic cancer and a type of skin cancer called melanoma in women who have mutations. Men with mutations in these genes also have an increased risk of developing several forms of cancer, including breast cancer, pancreatic cancer, prostate cancer, and melanoma. 

The proteins produced from the BRCA1 and BRCA2 genes are involved in fixing damaged DNA, which helps to maintain the stability of a cell's genetic information. They are described as tumor suppressors because they help keep cells from growing and dividing too fast or in an uncontrolled way. Mutations in these genes impair DNA repair, allowing potentially damaging mutations to persist in DNA. As these defects accumulate, they can trigger cells to grow and divide without control or order to form a tumor. The objectives of this research is to find out the genetic correlation between breast cancer and inheritance of mutated genes. Furthermore, this study will lead to collection of data from hospital and analyze the prevalence of breast cancer in Abbottabad region.

MATERIALS & METHODS:

 A retrospective observational study was carried out including patients who visited Atomic Energy Cancer Hospital (INOR), Abbottabad from March, 2018 to March, 2023. A total of 168 patients with biopsy proven Breast Carcinoma were included in the study. Data regarding patient’s age, gender, site of involvement, side of involvement, habits regarding tobacco usage, grading of tumor and patient’s address was collected on a structured proforma. Data were retrieved from the biopsy reports.

RESULTS:

168 Breast cancer patient’s data was retrieved and after going through their recorded history and biopsy reports. We found out that only 8 patients out of 168 had genetic mutations.  

Graphical representation of collected data on breast cancer

8 out of 168 female patients were recorded with genetic mutations in BRCA1 and BRCA2genes. 3 out of 8 had reportedly BRCA-1 mutations. 5 out of 8 had BRCA-2 gene mutation. 1 out of 3 patients with BRCA1 mutation, had age less than 40 years and 4 out of 5 patients with BRCA2 mutation, had age less than 50 years. Family history of different patients was also recorded.

We thoroughly observed family history of those 8 patients with BRCA1 and BRCA2 gene mutation and found out that 2 patients had no family history. 5 of them had family history of breast cancer and 1 of them had a mother and grandmother affected from breast cancer. Moreover, a 46 year old female patient had a paternal aunt with breast cancer. Percentage of  Genetic mutation in BRCA1 AND BRCA2 genes was 4.8%. Prevalence of BRCA1 mutation related breast cancer was 1.8% and prevalence of BRCA2 mutation related breast cancer was 3%.

CONCLUSION:

According to our findings, we observed that in the region of Abbottabad, the occurrence of genetically acquired breast cancer rate is much lower and most of the cases show somatic mutations. However, these findings show that  the probability of genetically inheriting the mutated gene is still 2-4% which is approximately close to the probability shown by other researchers i.e., 5-7 percent which was observed during our literature review. This study can lead to the innovation in breast cancer therapy by targeting mutated genes and can help to prevent the incidence of breast cancer.

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