Our study shows that there are no reliable clinicopathologic factors to predict the HER2 status in breast tumors with equivocal HER2 immunostaining, supporting the necessary usage of FISH in such circumstances.

Breast cancer is a serious worldwide public health problem and is currently the most common cancer overall. Its endocrine therapy is related to the expression of the steroid hormones, estrogen receptor (ER), and progesterone receptor (PR). Breast cancers can be presented under multiple profiles of steroid hormones: ER(−)/PR(+), ER(+)/PR(−), double-positive/negative ER, and PR. 2–8% of all breast cancers express only PR (ER−/PR+) which is an abnormal phenotype, with less known about their behaviors and outcomes. Our study was performed on a large and well-characterized database of primary breast cancer from 2012 to 2019, up to 1159 cases. These cases were divided according to ER and PR expression, as we put all of our focus on ER-negative/PR-positive group, more specifically ER−/PR+/HER2+ and ER−/PR+/HER2− gene expressions, to highlight their features and find a pattern that links HR (hormone receptors) profiles and breast cancer subtypes. Out of the informative cases, 94 patients (8%) had ER−/PR+ breast cancers, while 676 (58.4%) had ER+/PR+, 88 (7.6%) had ER+/PR−, and 164 (14.2%) had ER−/PR− tumors. The ER−/PR+ group was statistically correlated with a high risk of recurrence and death in midway between the double-negative and double-positive HR. According to HER2 status, a low DFS was observed in patients ER−/PR+/HER2−, which is closer to the DFS of TNBC cases but worse than ER+/PR any. On the other side, the ER−/PR+/HER2+ showed also a poorer DFS closer to the HER2+ subgroup in between TNBC and ER+/PR any. The clinicopathological features of the ER−/PR+/HER2− and ER−/PR+ HER2+ have distinguished the patients into two groups with a difference in some clinicopathological characteristics: both groups had closer OS estimation, which was worse than ER−/PR any and better than TNBC and HER2. The ER−/PR+/HER2− seems to increase the risk of recurrence than ER−/PR+/HER2+ when compared to ER+/PR any. On the other hand, the ER−/PR+/HER2+ seems to increase the risk of death more than ER−/PR+/HER2− in comparison with ER+/PR any. Our results support that ER−/PR+ tumors really exist and are rare and clinically and biologically distinct subtypes of breast cancer. In addition, our analysis, which was based on dividing the groups according to HER2 expression, has revealed the existence of two distinct groups; this gave the ER−/PR+ subgroup a heterogeneity characterization. Moreover, this breast cancer subtype should not be treated as a luminal tumor but rather according to the HER2 expression status.

Background: Breast cancer is a major public health problem worldwide. It's the most common cause of death from cancer in women, it considers a heterogeneous disease, shows variable morphological and biological features, they have different clinical behavior, and prognoses, and respond to therapy differently despite similarities in histological types, grade, and stage. The classication aims for an accurate diagnosis and prediction of behavior, however, histological classication isn't enough in this era of personalized medicine, this results in « overtreatment » of many patients, so, molecular proling allows tumors to be dened by the expression pattern or genomic alteration of thousands of genes. A Methods: retrospective, descriptive and analytic study was performed among 1040 women with invasive breast carcinoma, which was diagnosed in the department of surgical pathology at University Hospital Center of Hassan 2 of Fez in Morocco, during a period ranging from 2012 to 2019. The prevalence of different molecular subtypes of breast carcinoma was estimated, in addition, clinicopathological features such as age, tumor size, tumor grade, lymph node involvement, hormonal receptors prole, and HER2 status have been compared. The mean age of diagnosis was Results: 49.5 years (DS12,5 years, 17-88 years), among these, 637 (55%) were under 50 years. NOS invasive breast carcinoma was the histological type the most common in 1030 (89%), with an SBR II in 60% of cases. The Mean tumor size was 2.8cm. Axillary lymph nodes (LN) were metastatic in 60% of cases. 76% of cases showed positive staining for estrogen receptors, 75,5% for progesterone receptors, and 18,5% for HER2/neu. Luminal A subtype was found in 22% of patients while Luminal B was present in 62,5% of patients, HER2 enriched in 5%, and triple-negative (TN) in 10,5 % of cases. There is signicant difference between the 4 subclasses by age (P=0.02), SBR grading (p<0,0001), tumor size (p=0,05), lymph node metastasis (0,0001). There are more young women in HER2 enriched and luminal B subtypes than in luminal A and TN subtypes, while the rate of older women is increased in luminal A subtypes. The proportion of patients with histological grade III in the TN subtype and HER2 subtype, is signicantly increased (P<0.0001) while grade I is signicantly increased in the luminal A subtype. LN metastasis in the luminal B and Her2 cancers are more signicant than in luminal A and TN. Disease-free survival (DFS) among older women above 50 years is signicantly greater among young women under 40 years ( p=0,021). Regarding SBR grading, and DFS, we found that survival was signicantly highest for patients with grade I, followed by those with grade II and then grade III (P<0.0001). According to molecular subtypes, we noted that DFS was signicantly highest for patients with luminal-A subtype, followed by those with luminal B subtype, then HER2 and TN cancers (P<0.0001). The Conclusion: present study shows the particularities of women breast carcinoma in our countryo, through our results, we found that BC is diagnosed at a younger age, a decade earlier than in developed countries, and we found a predominance of luminal B subtype in contrary with others studies suggesting that there are clinico-biological differences, as well as disparities in the expression proling in our population. This highlights the importance of early screening and the need to improve women's awareness of breast cancer in our region and additional research is needed to understand these results in hopes of adopting more effective therapies.

Conclusions: Our results suggest that breast cancer patients with high CD326 + CD44 + CD24 -/low and p-Akt473 expression as well as with co-expression of CD221 + cells in tumor tissue were less sensitive to tamoxifen treatment. More detailed assessment of breast cancer stem cells markers and PI3K/Akt signaling components are required to investigate their clinical and prognostic efficacy.Legal entity responsible for the study: The authors.