Triple-Negative Apocrine Carcinomas: Toward a Unified Group With Shared Molecular Features and Clinical Behavior

Schwartz, Christopher J.; Ruiz, Jeanette; Bean, Gregory R.; Sirohi, Deepika; Joseph, Nancy M.; Hosfield, Elizabeth M.; Jacobs, Timothy W.; Mukhtar, Rita A.; Chen, Yunn-Yi; Krings, Gregor

doi:10.1016/j.modpat.2023.100125

Cited by 9 publications

(7 citation statements)

References 63 publications

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“…We summarized the genetic alterations from our study and by Schwartz et al 34 in Table 2, and similar findings were found, including GA in the PI3K-PKB/Akt pathway ( PIK3CA , PIK3R1 , and PTEN ), along with the Ras-MAPK pathway and TP53. In addition, our results are consistent with this study regarding patients’ clinical outcomes.…”

Section: Discussionsupporting

confidence: 80%

“…The PI3K signaling pathway controls various cellular processes, such as metabolism, proliferation, and apoptosis, and contributes to tumor development and progression. 36 We summarized the genetic alterations from our study and by Schwartz et al 34 in Table 2, and similar findings were found, including GA in the PI3K-PKB/Akt pathway (PIK3CA, PIK3R1, and PTEN), along with the Ras-MAPK pathway and TP53. In addition, our results are consistent with this study regarding patients' clinical outcomes.…”

Section: Discussionsupporting

confidence: 80%

“…Clinical trials failed to show significance in clinical treatment response of AR-positive versus AR-negative groups. [33][34][35] Recently, Schwartz et al 34 studied 41 patients with apocrine TNBCs, with 10 patients with NAC showing variable responses. Two patients with complete imaging response had a residual tumor on pathologic examination.…”

Section: Discussionmentioning

confidence: 99%

“…However, clinical outcome data were contrivosial in those LARs or TNAC groups. Clinical trials failed to show significance in clinical treatment response of AR-positive versus AR-negative groups 33–35 . Recently, Schwartz et al 34 studied 41 patients with apocrine TNBCs, with 10 patients with NAC showing variable responses.…”

Section: Discussionmentioning

confidence: 99%

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Triple-negative Breast Carcinoma With Apocrine and Histiocytoid Features

Wang¹,

Hacking²,

Graff

et al. 2023

American Journal of Surgical Pathology

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Triple-negative breast cancer (TNBC) is a heterogenous group of tumors. Most TNBCs are high-grade aggressive tumors, but a minority of TNBCs are not high grade, with relatively indolent behavior and specific morphologic and molecular features. We performed a clinicopathologic and molecular assessment of 18 non–high-grade TNBCs with apocrine and/or histiocytoid features. All were grade I or II with low Ki-67 (≤20%). Thirteen (72%) showed apocrine features, and 5 (28%) showed histiocytoid and lobular features. In all, 17/18 expressed the androgen receptor, and 13/13 expressed gross cystic disease fluid protein 15. Four (22.2%) patients were treated with neoadjuvant chemotherapy, but none achieved a pathologic complete response. In all, 2/18 patients (11%) had lymph node metastasis at the time of surgery. None of the cases had a recurrence or disease-specific death, with an average follow-up time of 38 months. Thirteen cases were profiled by targeted capture-based next-generation DNA sequencing. Genomic alterations (GAs) were most significant for PI3K-PKB/Akt pathway (69%) genes, including PIK3R1 (23%), PIK3CA (38%), and PTEN (23%), and RTK-RAS pathway (62%) including FGFR4 (46%) and ERBB2 (15%). TP53 GA was seen in only 31% of patients. Our findings support those on high-grade TNBCs with apocrine and/or histiocytoid features as a clinicopathologic and genetically distinct subgroup of TNBC. They can be defined by features including tubule formation, rare mitosis, low Ki-67 (≤20%), triple-negative status, expression of androgen receptor and/or gross cystic disease fluid protein 15, and GA in the PI3K-PKB/Akt and/or RTK-RAS pathway. These tumors are not sensitive to chemotherapy but have favorable clinical behavior. Tumor subtype definitions are the first step to implementing future trial designs to select these patients.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Triple-negative Breast Carcinoma With Apocrine and Histiocytoid Features

Wang¹,

Hacking²,

Graff

et al. 2023

American Journal of Surgical Pathology

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“…37,38 A significant subset of GATA3+ TNBC are apocrine carcinomas, where the majority express both GATA3 and GCDFP-15. 39 As GATA3 is critical for the development of tissue types across all germ layers, expression is present in a broad range of normal squamous and urologic epithelial cells, a subset of T cells, and a variety of malignancies, ranging from squamous and urothelial carcinomas, a subset of oncocytic renal tumors, 38,40 nearly all cutaneous adnexal neoplasms and approximately half of salivary gland tumors, with rare positive cancers in the liver and lung (frequent sites of breast cancer metastasis). When paired with appropriate immunostains, the "multispecificity" 38 of GATA3 can be leveraged to suggest a site of origin for a metastasis.…”

Section: Gata3mentioning

confidence: 99%

TRPS1, a New Promising Marker for Assessment of Distant Metastatic Breast Cancer

McIntire,

Duckworth,

Van Arnam

et al. 2023

Advances in Anatomic Pathology

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This article reviewed the identification of breast cancer in the distant metastatic setting through traditional immunohistochemical markers, such as mammaglobin and GATA3, compared with the novel immunohistochemical stain, Trichorhinophalangeal syndrome-1 (TRPS1). We review previous studies evaluating TRPS1 staining, which were conducted using cytology specimens, as well as our recently conducted study evaluating this stain using surgical tissue samples, both from primary and distant metastatic invasive breast carcinoma. In summary, although no immunohistochemical stain is 100% specific or sensitive, in the metastatic setting where tissue available for ancillary studies is limited, TRPS1 was a reliable and even a standalone marker for breast origin, particularly in cases of triple-negative breast cancer.

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