Gene expression analysis reveals a different transcriptomic landscape in female and male breast cancer

Callari, Maurizio; Cappelletti, Vera; Cecco, Loris De; Musella, Valeria; Miodini, Patrizia; Veneroni, Silvia; Gariboldi, Manuela; Pierotti, Marco A.; Daidone, Maria Grazia

doi:10.1007/s10549-010-1015-8

Cited by 84 publications

(69 citation statements)

References 55 publications

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“…Callari et al [16] compared gene expression profiles of 37 ER-positive MBC specimens to those of 53 ER-positive FBC specimens. Almost 1,000 genes were found to be differentially expressed in female and male patients, and biological interpretation highlighted a gender-associated modulation of key biological processes ranging from energy metabolism to regulation of translation and matrix remodeling as well as immune system recruitment [16]. Johansson et al [17] described two unique subgroups of MBC with differences in tumor biological features and outcome.…”

Section: Discussionmentioning

confidence: 99%

The 21-Gene Recurrence Score Assay (Oncotype DX™) in Estrogen Receptor-Positive Male Breast Cancer: Experience in an Israeli Cohort

et al. 2014

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Objective: The 21-gene recurrence score (RS) assay has been widely adopted for use in early estrogen receptor (ER)-positive breast cancer to assess the risk for distant recurrence and the potential benefit of adjuvant chemotherapy. The primary aim of this study was to assess RS distribution in Israeli male breast cancer (MBC) patients. Methods: The study population included 65 newly diagnosed Israeli MBC patients. Clinical and pathologic data were collected at the time of referral. Pathologic examinations were conducted at the pathology departments of the referring centers. The RS assay (Oncotype DX™) was performed on paraffin-embedded tumor samples at Genomic Health laboratories. Results: The mean age of the patients was 65.1 years (range 38-88 years). Low-risk (RS <18), intermediate-risk (RS 18-30) and high-risk (RS ≥31) scores were noted in 29 patients (44.6%), 27 patients (41.5%) and 9 patients (13.9%), respectively. The distribution of RS in male patients was similar to the distribution in 2,455 female patients from Israel referred during the same time period. Conclusion: Our data suggest that the distribution of Oncotype DX RS in ER-positive MBC patients is similar to that of female breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

The 21-Gene Recurrence Score Assay (Oncotype DX™) in Estrogen Receptor-Positive Male Breast Cancer: Experience in an Israeli Cohort

et al. 2014

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“…4 Other studies have also indicated a different role of steroid receptors in male breast cancer, suggesting a reduced functionality of ER. 30,31 Consequently, the ER stimulating effect of cyclin D1 may be limited in male breast cancer.…”

Section: Discussionmentioning

confidence: 99%

High proliferation is associated with inferior outcome in male breast cancer patients

et al. 2013

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Assessment of proliferation is important in female breast cancer and individual treatment decisions are based upon its results, especially in the luminal subgroups. Gene expression analyses fail to group male breast cancer into the intrinsic subgroups previously established in female breast cancer. Even though proliferation has been shown to divide male breast cancer into molecular subgroups with different prognoses, the clinical importance of proliferation markers has not yet been elucidated. Previous studies in male breast cancer have demonstrated contradictory results regarding the prognostic impact of histological grade and Ki-67, parameters strongly associated with proliferation. The aim of the present project was to study proliferation in male breast cancer by assessing other proliferation-related markers viz. cyclins A, B, D1 and mitotic count. A total of 197 male breast cancer cases with accessible paraffin-embedded material and outcome data were investigated. Immunohistochemical stainings were performed on tissue microarrays. Kaplan-Meier estimates and the Cox proportional regression models were used for survival analyses with breast cancer death as the event. The subset of patients with high expression of cyclin A (hazard ratio (HR) 3.7; P ¼ 0.001) and B (HR 2.7; P ¼ 0.02) demonstrated a poorer survival. Furthermore, high mitotic count was associated with an increased risk of breast cancer death (HR 2.5; P ¼ 0.01). In contrast, cyclin D1 overexpression was predictive of better breast cancer survival (HR 0.3; P ¼ 0.001). In conclusion, high levels of cyclin A and B expression and an elevated mitotic count result in a two to threefold higher risk for breast cancer death, whereas cyclin D1 overexpression halves the risk. The clinical utility of these proliferation markers needs further elucidation. Modern Pathology (2013) 26, 87-94; doi:10.1038/modpathol.2012.145; published online 24 August 2012 Keywords: breast cancer; immunohistochemistry; male Male breast cancer represents 0.6% of all breast cancer and because of its rarity, specific treatment guidelines are lacking. Thus, male patients are treated according to the guidelines for female breast cancer. Breast cancer mortality among women has declined during the last decades because of improvements in diagnostic procedures and treatment, but the corresponding observation has not been made in male breast cancer. 1 Recent studies have indicated that males have a poorer survival than females, despite having received adjuvant treatment to the same extent. 2,3 In addition, studies on transcriptional and genomic levels have revealed important molecular differences between male and female breast cancer. In a recent study, Johansson et al 4 performed gene expression analyses in male breast cancer and concluded that male breast cancer tumors could not be classified into the intrinsic subtypes previously established in female breast cancer. In line with these data, comparative genomic hybridization demonstrated significant differences regarding DNA aberrations com...

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“…Even though array data were exclusively interrogated, to our knowledge, for seven gene expression modules and a signature registering the activity of AR was not scrutinized, this study provided further ground to the heterogeneous nature of MBC. An independent gene expression profiling study carried to retrieve differences between MBC and FBC yielded approximately 1.000 differentially expressed genes [33]. Biological interpretation of this gene set revealed that a significant higher number of AR-related genes were up-regulated in MBC compared with FBC, and overall suggested AR activation.…”

Section: Ar In Mbc: Transcriptome-based Studiesmentioning

confidence: 99%

Androgen receptor and antiandrogen therapy in male breast cancer

et al. 2015

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Cancers arising in the male breast are uncommon. Male breast cancer is a hormone-driven disease that often expresses the estrogen receptor, and antiestrogen therapy represents the mainstay of treatment. Paradoxically, the advent of a wave of antiestrogens eclipsed the therapeutic potential of alternative therapeutic options. At the beginning of the hormonal therapy era the administration of antiandrogens to metastatic male breast cancer patients was proposed. Ever since the use of these compounds has largely been neglected. A therapeutic role for antiandrogens has been envisioned again in recent years. First, molecular characterization efforts pointed to the androgen receptor as a potential therapeutic target. Second, the development of aromatase inhibitors unexpectedly raised the need for neutralizing androgens in order to tackle endocrine feedback mechanisms responsible for acquired resistance. We herein provide an overview of molecular studies where the androgen receptor was investigated at the genomic, transcriptomic or phenotypic level. We then discuss androgens in the context of the endocrine networks nourishing male breast cancer. Finally, clinical evidence on antiandrogens is summarized along with strategies should be implemented to improve the medical management of these patients.

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Gene expression analysis reveals a different transcriptomic landscape in female and male breast cancer

Cited by 84 publications

References 55 publications

The 21-Gene Recurrence Score Assay (Oncotype DX™) in Estrogen Receptor-Positive Male Breast Cancer: Experience in an Israeli Cohort

The 21-Gene Recurrence Score Assay (Oncotype DX™) in Estrogen Receptor-Positive Male Breast Cancer: Experience in an Israeli Cohort

High proliferation is associated with inferior outcome in male breast cancer patients

Androgen receptor and antiandrogen therapy in male breast cancer

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