JOURNAL OF MEDICAL AND SURGICAL RESEARCH - Special Issue "Pathology", March, 2023

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The prognosis and predictive value of estrogen negative/progesteron positive (ER-/PR+) phenotype.

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Category: JMSR Pathology

Abstract:

Background: 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 (ER/PR). Breast cancers can be presented under multiple profiles of steroid hormones. 2–8% of all breast cancers express only PR (ER?/PR+) which is an abnormal phenotype, with less known about their behaviors and outcomes.

Methods: We collected a large and well-characterized database of primary breast cancer from 2012 to 2019, including 1159 cases. These cases were divided according to ER and PR expression, we focused ER?/PR+/HER2+ and ER?/PR+/HER2? subgroups, to highlight their clinicopathologic features.

Results: 94 patients (8%) had ER?/PR+ profile, while 676 (58.4%) had ER+/PR+, 88 (7.6%) had ER+/PR?, and 164 (14.2%) had ER?/PR- profile. 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 was closer to the DFS of TNBC cases but worse than ER+/PR any. On the other hand, the ER?/PR+/HER2+ showed also a poorer DFS closer to the HER2+ subgroup 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. 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.

Discussion: In our study, 8% of patients had presented the ER?/PR+ phenotype; this is consistent with the previously published cohort using ER and PR IHC. Our findings are similar to those already published such as younger age at diagnosis, poorly differentiated tumor and larger tumor size. On the other side, the separation into intrinsic subtypes by PAM50 test revealed that the vast majority of cases were of the basal subtype (53–65%), followed by the luminal A subtype (15–27%). It shares molecular features with TNBC. 90% of ER(?)/PR(+) tumors are characterized by low predicted endocrine sensitivity by the sensitivity to endocrine therapy (SET) gene signature, especially in “high-risk” cancers.

Conclusion: ER-/PR+ BCs really exist and it’s different from others subgroups BCs, its clinical molecular feature and behaviors midway between those of double positive and double negative, moreover, these distinction seems more important in the subgroup HER2 negative which is slightly similar to TNBC. So the question is treat or not treat with ET single PR+ BC, the response to this requires prospective studies and clinical trials in order to optimize the breast cancer‘s treatment in the era of precision medicine.

Full Text:

The prognosis and predictive value of estrogen negative/progesteron positive (ER-/PR+) phenotype.

Layla Tahiri Elousrouti, Sanae Gamrani, Hinde EL FATEMI

1-Department of Pathology, Hassan II University Hospital, 2- Biomedical and Translational Research Laboratory, Faculty of Medicine and Pharmacy, Sidi Mohamed Ben Abdellah University, Fez, Morocco.

Correspondence : Layla Tahiri Elousrouti;

mail: Layla.tahirielousrouti@usmba.ac.ma,

Orcid ID: https://orcid.org/0000-0002-2848-7549.

Background: 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 (ER/PR). Breast cancers can be presented under multiple profiles of steroid hormones. 2–8% of all breast cancers express only PR (ER?/PR+) which is an abnormal phenotype, with less known about their behaviors and outcomes.

Methods: We collected a large and well-characterized database of primary breast cancer from 2012 to 2019, including 1159 cases. These cases were divided according to ER and PR expression, we focused ER?/PR+/HER2+ and ER?/PR+/HER2? subgroups, to highlight their clinicopathologic features.

Results: 94 patients (8%) had ER?/PR+ profile, while 676 (58.4%) had ER+/PR+, 88 (7.6%) had ER+/PR?, and 164 (14.2%) had ER?/PR- profile. 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 was closer to the DFS of TNBC cases but worse than ER+/PR any. On the other hand, the ER?/PR+/HER2+ showed also a poorer DFS closer to the HER2+ subgroup 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. 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.

Discussion: In our study, 8% of patients had presented the ER?/PR+ phenotype; this is consistent with the previously published cohort using ER and PR IHC. Our findings are similar to those already published such as younger age at diagnosis, poorly differentiated tumor and larger tumor size. On the other side, the separation into intrinsic subtypes by PAM50 test revealed that the vast majority of cases were of the basal subtype (53–65%), followed by the luminal A subtype (15–27%). It shares molecular features with TNBC. 90% of ER(?)/PR(+) tumors are characterized by low predicted endocrine sensitivity by the sensitivity to endocrine therapy (SET) gene signature, especially in “high-risk” cancers.

Conclusion: ER-/PR+ BCs really exist and it’s different from others subgroups BCs, its clinical molecular feature and behaviors midway between those of double positive and double negative, moreover, these distinction seems more important in the subgroup HER2 negative which is slightly similar to TNBC. So the question is treat or not treat with ET single PR+ BC, the response to this requires prospective studies and clinical trials in order to optimize the breast cancer‘s treatment in the era of precision medicine.

Key words: breast cancer; immunohistochemistry, estrogen negative/progesteron positive phenotype, prognosis.

References:

1. E. A. Rakha, M. E. El-Sayed, A. R. Green et al., “Biologic and clinical characteristics of breast cancer with single hormone receptor-positive phenotype,” Journal of Clinical Oncology, vol. 25, no. 30, pp. 4772–4778, 2007.
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