Pilot Study of Breast Cancer Patients with a Long Term Follow up in Erbil-Iraq

Background: Breast cancer remains as the most common malignant neoplasm in females and one of the main life-threatening diseases, this long-term follow-up study under run for patients of carcinoma of the breast. Objective: To gain practical feedbacks from the progression and fates of the patients who had been managed by the standard is previously known international guidelines. Patients and Methods: This retrospective study involved (40) breast cancer cases In Erbil-Iraq for more than 15 years. Checkup tools were clinical examinations, laboratory investigations, and images for recurrence and metastasis. The following parameters had been studied; Age, clinical presentation, histopathological diagnosis, staging and management including surgeries, further adjuvant therapies and survival rates by periodic follow-up both in hospital and home visits. Results: The results of this study showed that the left breast affected more frequently by 2:1 than the right. In 85% of patients, 1st presentations were in the 1-3 months and in stage II. Age's distribution was mainly between 31-60 years. Only 6 (15%) cases showed positive family history. The most common histopathology type was infiltrative ductal carcinoma 27(67.5%) and the prominent grades were (GII and GIII). Molecular based distribution of (Luminal B) was the biggest immunohistochemical type. About 70% of the cases were managed by quadrectomy or simple mastectomy and/or Axillary clearance. By (15) years follow-up (42.5%) cases lived between 5 to 10 years, and another (17.5%) survived above 10 years. No relation found between the cope of patients with her malignancy and course of the disease. Conclusion: In the future, we have to concentrate on middle age and more scientific as they are by with advanced searching management routes. Older patient’s carcinoma convention was less aggressive than younger, their life expectancy longer after diagnosis and treatment options. In the young group patient's tumor was more aggressive. Anyhow, breast cancer character remained unpredictable for various involved factors complexity and physiological variability of females. Recurrences, metastasis, and survival depend on familial and environmental code factors. Delay diagnosis is still a disaster in this locality that interferes with better results.


Introduction
Breast cancer, which is considered to be the most prevalent female malignancy, and is the main cause of death in middle-aged women and its incidence is elevating [1]. Internationally breast cancer is the second most common cancer in the world and represents 9% of the global cancer burden. The malignant breast neoplasms are usually caused by their abnormal growth and uncontrolled proliferation of epithelial cells within the terminal duct and lobular parts of the breast [2]. Changes or mutations in DNA can cause normal breast cells to become cancer. Certain DNA changes are inherited and can greatly increase risks for breast cancer. Others are environmental causes that induce DNA mutation. But it's not yet known exactly how some of these risk factors cause normal cells to become cancer [1,2]. However, in patients with a suggestive personal and or family history, a specific predisposing gene is identified in <30% of cases [2]. Hormones seem to play a role in many cases of breast cancer, but just how this ensues is not fully understood but epidemiological and experimental evidence implicates estrogens in the etiology of breast cancer [3]. The cancerous cells can attack and destroy surrounding normal tissue, and spread throughout all parts of the body including the bones via bloodstream or lymph fluid to metastasize to new sites [4].
However, the metastasis time and site is still unpredictable and variable in various patients, newly found special mutated genes responsible for that [4,5] it has been proposed that breast cancer is a multifocal and multifactorial disease and its etiology is interaction of the genetic and environmental factors [5]. Almost 90% of breast cancers occur sporadically, but without known predisposing genetic alterations, the remaining 10% are linked to genetic causes which include mutations in tumor suppressor genes, mostly BRCA1 and BRCA24.The incidence of breast cancer depends on the regions and countries, likely due to differences in racial and ethnic make-up, economy and social situations health resources, and lifestyle patterns [2].
With the introduction of molecular carcinoma cell subtyping the key of managements and prognosis is changed as the integration of morphological with molecular data has the potential to refine breast cancer classification, predict response to therapy, enhance understanding of breast cancer biology, and improve clinical management.
The early presentation, thorough approach and follow-up, experiences, team therapy and regarding all breast lumps malignant until proved otherwise moreover to ongoing researches and studies may restrict missing cases and entangles of diagnosis.
This study aimed to gain practical feedbacks from the progressions and fates of the patients who had been managed by standard international guidelines. To point out application deficiencies. To rearrange the next steps for more convenient future management.

Patients and Methods
In this revision (40) female breast cancer cases studied from May 2000 till December 2016 in which majority of them presented Vol. 19.Issue 2,December 2020 Pilot Study of Breast Cancer Patients with a Long Term Follow up in Erbil-Iraq Suhel M Esmael Najjar with breast mass managed by a detailed history of first symptoms, duration, stature, full family history, marital status, pregnancies, contraceptive pills, economic conditions, behaviors, residency. Followed by non-invasive ultrasonography imaging then mammography with or without MRI, followed by FNAC cytology then standard malignant dependent surgical procedure performed according to their condition and after discussion by the management team of pathology, genetics, and oncology to the patient herself or and first-degree relative. The surgery took place in Rizgary teaching and Zheen international hospitals, by a team of two surgeons and anesthetics group, with the presence of histopathologists. Patients remained in the hospital for 3-5 days discharged home with further out-patient follow-up. The excised samples sent for laboratory for histopathological and immunohistochemical (ER, PR, Her2) studies were performed then the patients were referred to oncologist according to standard protocols and they were rechecked periodically during and after finishing adjuvant chemo and or hormonal therapy. The follow up was monthly first 6 months, then every three months. Visitings after 12 months became every three months and then every six months. Follow-up also took place according to the patient's needs intermittently. Most visits were in the breast clinics and fewer in the patients' homes.

Statistical analysis
Categorical and continuous variables were compared using (independent t-test) and identified standard deviation using Microsoft SSPS version 19 to measure P-value. When P-value was less than 0.05 regarded as significant, less as 0.01 highly significant, and above 0.05 regarded non-significant.

Results
From observed that early presentation of the patient is still not well established educationally as 20 cases (50%) presented beyond the first stage.
Table (1) showed that the major presenting symptom of breast cancer (BC) was a lump (80%) or localized mass rather than other symptoms. The incidence of BC was more in the left breast than right observed by this Figure (1 Table(2) we notice the late presentation of the patient predominant, as the patients searched clinical intervention after 1-3 months after appearing of their early symptoms and presented after their BC became prominent  The results of this study showed that most of the patients (ages up to 40) were presented in stage III followed by stage II, then stage I, regarding ages above 41 years greatest cases was in stage II that was 18 (45%) patients then followed by stage III which was 15 cases (37.5%) Figure (4). However sporadic cases attended in earlier or late stages.   By observing Figure (6) About 6 cases (15%) showed positive family history, and religious distribution is nearly equal in comparison to religious demographic distribution and no significant provoking effect is seen and Pvalue as it was more than 0.07.

Figure (6): Family history & religion
Regarding the operation types used as seen in     (7) showed that 17 (42.5%) of the cases are survived for more than 5 years and 7 ( 17%) patients more than 10 years and 13 (32.5%) of cases died before the continuation of 5 years survival.

Discussion
For many years, there has been a widespread impression among clinicians that breast cancer in younger women is an aggressive disease, whereas among older women (≥ 60 years) the disease has a more indolent nature. This study has, to some extent, supported these ideas that all nine cases less than 30 years died within the first five years of follow-up. While tumors known to have an aggressive nature occur in all age groups, the increased incidence of grade III cancers among younger women does suggest a less favorable prognosis for this age group [6,7].
In this study the left breast more attacked by carcinoma, this phenomenon also mentioned by other studies as breast cancer is more common in the left breast than the right. The left breast is 5 -10% more likely to develop cancer than the right breast, the cause till now is unknown [7,8].
The peak ages were affected included 41 to 61 years, this may fulfill mentioned international map of age distribution but lastly, some younger ages are also observed, putting in mind that last ten years included these young ages which correlate the wear and tear stress of the area conditions as blamed to be cause for breast cancer although studies result for stress effects on carcinoma of breast are non-conclusive [7,10]. While (Yujing J Heng et al 2017) as a Japanese study cited that young ages are frequently affected but we found nearly young and olds are affected evenly and non-significantly older ages more same idea confirmed by (Deng C. X -2006) [9,11].
The majority of cases in this study were stage 2(48%), stage 3(43%) and then stage 1(9%). Such findings have also been documented in some Arabic countries, while in developed countries; most patients may present with early stages and may be ticked during ordinary breast screening [9,10,11].
The delays as also mentioned by (E. Donald et al 2003) are mainly due to the lack of perfect health education, delay medical consultation, absence of perfect health system of screening, rejection of management strategy, and defects in a follow-up. This result was also in agreement with a study in Iran which concluded that stage II is the most prevalent followed by Vol. 19 [14]. A young patient attended in stage-4 the husband blamed the unavailability of a female doctor in this specialty (religious Custom). Anyhow this is regarded as one of the causes of delayed presentation [14,15].
Molecular based classification this studies triple-negative model predominance in the cases are analogous with the internationally mentioned heterogeneity of breast cancer cases, and showed GIII nature tumor cells [14,15,16]. We found a strong correlation between female residency and environmental influences on breast carcinoma but special studies in this regard either missing or controversial [18,19]. The recurrences were as usually mentioned by various references included: cases of pulmonary invasions, cases of liver metastasis, a case of thoracolumbar vertebral invasion, and two cases of brain metastasis by these metastases we observed correctness of idea proposed that breast cancer is intrinsically a systemic disease. New molecular technologies, such as DNA microarrays, support the idea that metastatic capacity might be an inherent feature of breast tumors [19,20].
Observable unpredictability of breast carcinoma with a variable period of time developed metastasis and died. This may indicate that the metastasis is a basic carcinoma genetic map dependent more than the environmental severity of toxication [21,22,24]. As we observed from basic molecular classification the triple-negative cases were predominant which indicates heterogeneity and aggressiveness of the tumor's cellular character and by grading distribution were grad-3 theses are normal to each personal and carcinoma cell character moreover to early diagnosis [18,21,23].

Conclusions
In this study, we concluded the following: 1. In this country, breast cancer was diagnosed in late-stage due to a lack of education of females. 2. If patients were treated properly even in the second stage the prognosis is amnestic and aggressive surgical operations were not essential. 3. Although genetic factors are blamed in all researches as 10% of causes of carcinoma of breasts, but in this study, well-observed environmental and stress factors are encountered more and blamed. 4. No relation and course changes observed by type of patients coping with carcinoma of the breast.

Recommendations
Management methods till now are only symptomatic and palliative, an original mother cell carcinoma genetic reformatting is the only radical treatment which is optimized and required. Accordingly most of our future studies should concentrate on genetic researches and team working.