Outcome of inflammatory breast cancer in Moroccan patients: clinical, molecular and pathological characteristics of 219 cases from the National Oncology Institute (INO)

Breast cancer is the most prevalent malignancy in women with more than a million and half new cases diagnosed annually [1].

Inflammatory breast cancer (IBC) is however uncommon, and considered as a rare type of breast cancer. Usually misdiagnosed, IBC is the most aggressive form of non-metastatic breast cancer [2]. IBC is characterized by rapid proliferation and several skin changes such as redness, orange skin, edema, ulceration and warmth [3, 4]. The diagnosis of this disease is based on clinical characteristics. Despite all intensive treatments, this study population still shows a very low survival rate [5]. IBC is usually associated with negative hormone receptors especially Estrogen receptor, positive Human Epidermal Growth Factor Receptor-2 (HER2), advanced stages and more metastasis [6].

IBC is more frequent in North Africa with 5% in Morocco, 6% in Tunisia and 11% in Egypt, while in America, only 2.5% of breast cancers are classified as IBC [6‐9]. These striking differences in IBC frequencies around the world are still misunderstood. In spite of all the scientific advances in medical research tackling this disease, the identification of risk factors directly related to IBC is inconclusive. Studies suggest that infectious agents, primarily Mouse Mammary Tumor Virus, represent the most probable etiology [10, 11]. Various studies have reported the suspicion of risk factors such as exposure to exogenous hormones, high fat intake, ethnicity, young age, heredity and socio-economic level [12‐15]. Still, none of these etiological factors have been proven to be directly linked to IBC.

IBC is still under-studied in Morocco, and to our knowledge, only one published study on this special breast cancer entity is counted [7]. For this reason, we have conducted this relatively large retrospective study of inflammatory breast cancer patients diagnosed at the National Oncology Institute (INO) in Rabat. This study aims at describing clinicopathological features, molecular characteristics and risk factors in a set of Moroccan inflammatory breast cancer patients over a period of 5 years and at analyzing prognostic factors and survival.

In this study, we have intended to investigate IBC’s clinical, molecular and pathological features, and analyze survival in Moroccan patients diagnosed with IBC between 2005 and 2010.

IBC is more frequent in North African countries, especially in Tunisia and Egypt where frequencies are 5 and 6% respectively. In our series, the frequency of IBC cases was 4.05%, which agrees with a previous study conducted at the same institute where authors have found an occurrence of 5% of all breast cancer cases [7].

A number of important epidemiological studies have found that IBC occurs at a younger age than non-inflammatory breast cancer [10]. Indeed, 65.3% of our IBC patients were younger than 50 years, while in Algeria the percentage was 59.8%. On the other hand, the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program has shown that only 34.7% of IBC patients were aged less than 50 years [20]. We have also noted some differences in median age between Algerian, Tunisian, Moroccan and American IBC series. Tunisian patients represent the youngest age with a median age of 43.5 years [21], followed by Moroccan and Algerian patients with a median age of 47 years and 48.5 years, respectively [7, 22]. Whereas American patients from the SEER program have shown the higher median age, 56 years [20]. These comparisons show that IBC might occur at younger age in North African populations compared to the American one. We may explain these differences by the possible viral etiology especially Mouse Mammary Tumor Virus Like (MMTV-Like) as described in previous studies led in this area [23, 24].

IBC diagnosis is entirely clinical and well established by AJJC; it is based on the presence of inflammatory signs especially diffuse erythema and oedema of the breast with or without an underlying mass. In the present study, palpable mass was detected in only 25.1% as compared to the Algerian series where it was detected in 31.9% of patients, while in Tunisian patients, the majority of women (76%) had palpable mass at the time of diagnosis [21, 22]. Once again, the Tunisian population shows a different aspect from the Algerian and Moroccan populations.

High BMI is considered as a risk factor for IBC and has been analyzed in several studies but the results are not conclusive [12, 21, 25, 26]. In the Tunisian series, 42% of IBC patients were obese while in our study we have registered a percentage of 34.1%. Data from the Breast Cancer Surveillance Consortium (BCSC) shows that 32.2% of IBC patients had a high BMI [26]. In a French study, we note that IBC patients are less obese, and only 21% of patients presented high BMI [12]. Furthermore, results from a comparative study between North-African series show no significant difference in BMI between IBC and non-IBC patients, but the authors still insist on the need for further studies because of the increasing incidence of obesity among women in North Africa [27].

IBC is known to show pejorative pathological characteristics. Therefore, we have found that 84.3% of the tumors measured more than 2 cm in greatest diameter, which joins the Algerian study findings with 88% of large sized tumors [22]. High SBR grades (SBR II and SBR III) were found in 92.9% of our IBC patients, 80.2% of SEER population [20], 76% of Tunisian patients [21], and 100% of Algerian and Egyptian patients [22, 27]. The comparative study between North African countries (Egypt, Tunisia and Morocco) demonstrate no statistical difference regarding SBR grades [27]. At the molecular level, many studies have documented that IBC is usually correlated to negative hormone receptors and positive HER2 status, which confers to this disease its aggressiveness [2]. The Tunisian study has shown that 52% of IBC tumors were ER-/PR- [28], while in Egypt only 38.9% of the tumors were negative for hormone receptors [27]. The lack of expression of hormone receptors in the Algerian study was 26.7% for ER and 71.8% for PR [22], while in our study IBC tumors were ER- in 44.4% and PR- in 30.3%. According to the comparative study, these disparities between North African countries did not show a significant difference [27].

Studies suggest that about 20~ 40% of IBC cases are triple negative breast cancers [2, 22, 29], which has a worse prognosis and lower survival rates than other breast cancer subtypes. Our study has shown the same range with 21.6% of TNBC tumors, and EFS was also at a lower rate in the TNBC subgroup compared to the other molecular subgroups with a significant difference (p = 0.02). The investigation of the seven triple negative subtypes, as described in Lehmann study (basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL), luminal androgen receptor (LAR), and unstable (UNS)), could contribute to resolving the differing clinical behavior when IBC and TNBC coexist [30, 31].

Interestingly and as in the Algerian study [22], the most prevalent subtype in our series was Luminal A followed by luminal B HER2+, unlike the Tunisian study where the most prevalent subtype was TNBC followed by HER2 subtype [32]. Molecular differences between these neighboring countries might be due to environmental and genetic factors that vary from an area to another. Further collaborative studies between these countries are needed.

The role of adjuvant endocrine therapy in the survivorship of IBC patients was clearly investigated in several clinical trials and concluded that SERM treatment is as efficient as chemotherapy in premenopausal breast cancer patients [21, 33]. Our study as well as the Tunisian one shows a significant better EFS in IBC patients who received adjuvant SERM treatment [21].

Contrastingly, the survival rates are higher in our series compared to the Tunisian study. In fact, the 3-year OS and EFS in our series were 70.4 and 46.5% respectively, while in Tunisia rates were 44 and 28%, respectively. This difference is mostly due to the lack of supportive care services and the absence of access to new drugs such as taxanes during the 1990’s, which corresponds to the period of study in Tunisian series [21].

Our study has several strengths. First, the number of patients with IBC is relatively large. Second, the large period that was taken to select participants extended over 6 years. Furthermore, our study represents the first large study including clinical, epidemiological, pathological and molecular characteristics of IBC in Moroccan patients.

This study has also limitations due to its retrospective aspect. Lack of data in some parameters is the major limitation. In addition, the study has been conducted in a single institution. Although it is the reference center of oncology in Morocco, our patients are not representative of the population. We also believe that short median follow-up and loss to follow-up rates could have influenced our survival rates. Finally, socioeconomic conditions have not been investigated, which might have limited access to some drugs like taxanes and Trastuzumab.

IBC in Morocco shows similar characteristics to those in North African countries; however, survival rates are still the highest when compared with neighboring countries. Collaborative studies with prospective aspects are warranted to establish the epidemiological profile and understand the high frequencies of IBC in North Africa. More studies on molecular markers are also needed to improve IBC patients’ management and eventually their survival rate.