Mbonde, Martin Philip2019-07-252020-01-082019-07-252020-01-082002Mbonde, M. P. (2002) A pathological study of carcinomas of the female breast in Tanzania, Masters dissertation, University of Dar es Salaam. Available at (http://41.86.178.3/internetserver3.1.2/detail.aspx)http://localhost:8080/xmlui/handle/123456789/6164Available in print formCarcinoma of the breast is the second most common malignancy in the African female. In these patients this malignancy occurs about a decade earlier and shows a more malignant histological picture and aggressive clinical course than in their counterparts in the developed countries. It had not been previously investigated if this behavior was an inherent characteristic presenting feature of this malignancy in the African female or was accrued during the long history of the disease prevalent in sub-Saharan African patients. Further, benign breast lesions had not been previously investigated for their potential as a source of breast cancer in African patients and the probable contribution of the resultant malignancies to the reported more aggressive behavior of this malignancy. This study aimed to investigate the histological presentation and risk of progression to carcinoma of benign lesions of the breast encountered in Tanzanian patients. It also investigated the expression of markers of tumor aggressiveness in carcinomas of the breast and compared them to literature reports. In addition, the influence of these markers to treatment response and survival of the patients was investigated. Materials for this study were routine biopsy and mastectomy tissues consisting of 63 benign lesions of the female breast and 184 breast cancers collected between 1990-1993, and 1989-1993, respectively. Tissues were formalin fixed and paraffin embedded and were recovered from the archives of the Department of Pathology, Muhimbili Medical Center, Dar es Salaam, Tanzania. The formalin fixed paraffin embedded tissues were used in the assessment of histology and DNA ploidy by flow-cytometry. In addition 96 fresh breast cancer tissues were prospectively collected between 1994-1997 and 1999-2000. The fresh frozen tissue was used to determine the expression of the following markers of tumor aggressiveness by immunohistochemistry: estrogen and progesterone receptors, proliferation rates (Ki-67}, p53 tumor suppressor and bcl-2 antiapoptotic proteins, proteinases Cathepsin D (Cath-D), urokinase plasminogen activator and its receptor urokinase plasminogen activator-receptor. Results showed that fibrocystic disease (FCD) (43%) and fibroadenomas (FA)(41%) were the most frequent benign lesions. Twenty-two percent of FCD patients showed proliferative lesions. The epithelial component in FA tended to atrophy as the lesions grew older, suggesting they were an insignificant risk as a source of carcinomas. Excision of this lesion on the basis of its probable risk of progression to malignancy is probably not justified. Histological types of breast cancer and their proportional composition as encountered in African patients was found to differ from that reported in Western females. An interesting feature in Tanzanian females was that the cribriform type (14. I %) was the most frequent ST tumor component in the studied cases. In addition, when compared to Western females, both NST and ST tumors tended to be of higher grades. Another distinguishing feature in this study was that 80% of the tumors were diploid and 20% aneuploid, whereas in Western females about 32% were diploid and 60% aneuploid. Remarkably low ER (36.5%) and PgR (19.8%) expression frequencies were found in this study when compared to reports in African-Americans and even higher in White females. Long disease duration, advanced disease stage, greater proportions of high histological grade tumors and genetic or racial factors are considered to be the causes of the differences. Another interesting observation was that the proportion of tumors negative for ER and PgR were lowest in patients when the disease duration was less than 6 months. After this duration the proportion of ER and PgR positive tumors increased and after 36 months only hormonal receptor positive tumors were encountered. In addition, bcl-2 was similarly related to disease duration as hormonal markers and that after 36 months disease duration all tumors co-expressed hormonal markers and bcl-2. This suggests that patients whose breast cancers expressed hormone receptors and bcl-2 tended to survive longer. Median proliferation rates as determined by IHC were 12.5% and the frequency of bcl-2 expression of 47.9% did not differ from literature reports. In addition breast cancer patients who survived longest had tumors which expressed bcl-2, these tumors also tended to have proliferation rates which increased with disease duration. Despite the proliferation rates increasing with disease duration the patients who expressed hormonal markers and bcl-2 seemed to survive longer. There was a lower frequency of expression of proteolytic enzymes in cancer cells: Cath-D, 10.4%. UPA, 35%, uPA-R, 33.3%. In contrast there was a high expression of Cath-D in stromal macrophages (82%) whereas uPA was encountered in only 3.7% in this compartment. There seemed to be a strong spatial association between stromal macrophages expressing Cath-D and stromal degradation, suggesting that Cath-D rather than uPA is the main participant of stromal degradation. Follow up of patients showed a short survival. Patients who received either surgical treatment, local radiotherapy or antihormonal therapy appeared to have a better recurrence and metastatic free survival in the short term but a poorer one in the long term. Also estrogen receptor positive status appeared to have a positive predictive value of response to therapy. In addition radiation oophorectomy, local-regional radiotherapy and mastectomy decreased the frequency of local breast cancer recurrences and increased the metastatic free survival. Contrary to expectation, bcl2 did not significantly decrease breast cancer response to anticancer therapy and seemed to be a marker of good rather than bad prognosis. UPA-R rather than Cath-D seemed to have greater prognostic benefit. Further studies are needed in order to confirm these findings. In conclusion, these studies show that Tanzanian and most likely other African breast cancers seem to have some biological differences in comparison to Western patients. The currently used patient management protocols seem to be appropriate for breast cancer patients in the short term. Adjuvant chemotherapy is advised in order to improve long term survival.enBreast cancerCancerClinical pyschologyTanzaniaThesis