Chronic Mastitis In North Africa: Geographic Overlap And A Potential Precursor Comorbidity Of Inflammatory Breast Cancer

Abstract North African countries, such as Egypt and Morocco, have a high prevalence of non-infectious, chronic mastitis (up to 10% of patients presenting with breast problems) compared to less than 1% worldwide. This same geographic region also suffers from an unusually high prevalence of inflammatory breast cancer (IBC) - 10-15% of breast cancer cases - versus just 1-2% of cases in the U.S. IBC is a serious public health issue as it is the most lethal form of breast cancer because of the propensity for rapid onset of disseminated metastases, which are present in one-third of cases at diagnosis. It is our hypothesis that this geographic overlap is not coincidental, but that the high level of background chronic breast inflammation changes the mammary microenvironment making it more auspicious for the development of IBC. Here we report our work aimed at determining molecular and histologic criteria to classify mastitis into pathogenic groups in order to rationally guide treatment for this serious inflammatory illness, as well as study its possible role in the development of IBC. We identified 44 cases of chronic mastitis of unknown etiology. Cases were defined as any female patient with histopathological diagnosis of chronic mastitis seen at the 5 study hospitals in Egypt and Morocco from 2008-2011. Exclusion criterion was previous diagnosis of malignancy. Biopsy slides were analyzed by a pathologist and stained for IgG4 and IgG. Out of the 44 cases of chronic mastitis using consensus guidelines and our molecular IgG4 profiling, we identified 10 as idiopathic granulomatous mastitis (IGM) and 17 as breast manifestations of IgG4-related disease. IGM is a rare non-neoplastic, chronic, often severe inflammatory lesion of the breast that mimics carcinoma clinically and radiologically. Treatment strategies include watchful waiting, immunosuppressive therapy, wide local or other excisions, or combinations of the above. IgG4-related disease is a newly recognized fibro-inflammatory condition. It is characterized by the formation of tumefactive lesions, a dense lymphoplasmacytic infiltrate with many IgG4-positive plasma cells, storiform fibrosis, obliterative phlebitis and, frequently, elevated serum IgG4 concentrations. While no randomized clinical trials have been conducted, glucocorticoid treatment is the standard first line therapy and appears to be quite effective in the majority of patients. This series is the largest reported and is the first step toward changing the chronic breast inflammatory landscape in North Africa by classifying the chronic mastitis into pathogenic groups that can guide personalized treatment protocols. Further studies are needed to discern whether effective and timely treatment of these chronic inflammatory conditions may lower the incidence of IBC. Citation Format: Steven G. Allen, Hanna Oltean, Kathy Toy, Omar S. Omar, Tamer Youssef, Mehdi Karkouri, Azza Abdel-Aziz, Ahmad Hablas, Ali Tahri, Celina Kleer, Amr Soliman, Sofia D. Merajver. Chronic mastitis in North Africa: Geographic overlap and a potential precursor comorbidity of inflammatory breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4977. doi:10.1158/1538-7445.AM2014-4977