Triple receptors-negative breast carcinoma

Clinical History

A 39 year old female consulted for a palpable left breast mass.

Imaging Findings

The mass was firm, painless, adherent to the deep plans, and located in the upper internal quadrant.
The mammography confirmed a voluminous round mass in the posterior third of the left upper internal quadrant (Fig. 1). Ultrasound depicted a solid hypoechoic mass, measuring 5,5x5,5x 4,3 cm (Fig. 2).
Core biopsy revealed poorly differentiated invasive ductal carcinoma, with high mitotic grade (Fig. 3). Immunohistochemical staining demonstrated absence of oestrogen receptors (ER), progesterone receptors (PR), human epidermal growth factor receptor (HER) 2, and HER1/epidermal growth factor receptor (EGFR) as well as strong positivity for cytokeratin 5 thus classifying this tumour as triple negative-receptors breast carcinoma of the basal subtype.
Breast MRI portrayed a unifocal posterior mass (Fig. 4-6). The mass exhibited well-defined borders, small areas of very high signal on T2, internal enhancing septations and continuous enhancement at delayed phase (persistent curve). The tumour did not invade the thoracic wall (Fig. 5,6).
Owing to the large dimensions of the tumour, neoadjuvant chemotherapy was administered. A regimen of 5-fluorouracil, epirubicin, ciclophosphamide combined with paclitaxel was chosen due to the immunohistochemical profile.
MRI assessment, at mid and end of chemotherapy, demonstrated minor concentric tumour shrinkage, corresponding to a minor response.
Left upper inner quadrant lumpectomy with axillary dissection was performed. The pathology's specimen closely related to the MRI features (Fig. 8) and confirmed the minor tumour response (tumour size - 4,5x4 cm). Both the surgical margins and the lymph nodes removed were tumour-free. The pathologic stage was pT2N0M0. Radiotherapy was started 1 month after surgery.

Discussion

Breast carcinoma encompasses a wide spectrum of malignancies with specific prognostic and therapeutic implications. Indeed, histologically similar tumours may have different prognoses and therapeutic responses due to molecular differences^1-4. Five molecular phenotypes have been demonstrated by microarray profiling: luminal A, luminal B, normal breast–like, HER2 overexpressing, and basal-like^1-4. Microarrays use in clinical routine is precluded for technical reasons. Immunohistochemical profiling has been adopted as a more feasible surrogate. Indeed, immunohistochemical marking ER-negative, PR-negative, HER2-negative, plus cytokeratin 5-positive and/or HER1/EGFR-positive is 76% sensitive and 100% specific for basal-like subtype diagnosis^3,4.

Triple receptors-negative carcinoma is a more generalist designation that refers to the lack of hormone receptors and HER2/neu staining. They have distinctive pathologic features, typically exhibiting a higher histologic grade, elevated mitotic count, central necrosis and fibrosis, pushing margins, scant stromal reaction, stromal lymphocytic response, and ductal or mixed histology with overrepresentation of unusual histologies (metaplastic, medullary, or adenoid cystic carcinomas)^1,4,5. Triple-negative carcinoma is in itself a heterogeneous group, encompassing at least two subcategories, the basal-subtype (60%) and the less well-defined nonbasal/multiple marker negative subtype^2,4,5.

Triple-negative carcinomas account for 16% of breast cancers in non–African American and 27% in African American women^4,6. They represent a diagnostic and therapeutic challenge because of their aggressive biology, late presentation (interval or large size cancers), and lack of hormonal and HER2/neu receptors which precludes targeted chemotherapy (hormonal or trastuzumab) and renders systemic therapy (usually anthracycline and/or taxane-based) the mainstay of treatment^2-4,7,8,. Triple-negative carcinomas are associated with younger age of onset, BRCA1 mutation carriers, and poorer prognosis, with a distant metastasis-free survival rate of 71% at 5 years^2-4,7,8. Nevertheless, these patients are radio-sensitive and candidates to breast-conserving therapy, with local relapse rate comparable to other subtypes. Due to its frequent large size at presentation, these patients benefit from neoadjuvant chemotherapy with a high response rate thought its molecular variability underscores the need for targeted drugs, possibly DNA damaging agents as platinum^4,5,7,8.

Although triple–negative cancers have large size at presentation due to rapid carcinogenesis, they frequently lack classic malignant features and risk being mistaken for benign lesions on mammography or ultrasound^4,9-12. They typically are manifested by an unifocal, dense, round or oval mass with smooth margins. The mass is often markedly hypoechoic with posterior acoustic enhancement and endotumoural vascularisation demonstrated on colour Doppler imaging. Calcifications are rare.

MRI provides a reliable baseline, accurately detecting local and contralateral extent, thus optimizing prognostic and therapeutic prediction as well as neoadjuvant chemotherapy response monitoring, particularly in the early setting and preoperative planning^7,8,13. Although triple-negative cancer can mimic benign morphology, a unifocal mass, smooth margin, heterogeneous rim-enhancement, central contrast-enhanced septations, washout or persistent enhancement pattern, and very high signal on T2 have been associated to a high positive predictive value for triple-negative cancer diagnosis^11-14. These MRI features clearly parallel triple-negative cancer histologic and biologic specificity.

The case presented nicely demonstrates the molecular and biological diversity as well as the distinctive mammographic, ultrasound, and MRI features of triple-negative breast carcinoma. In addition, the MRI role on posterior breast masses staging is exemplified.

Differential Diagnosis List

Final Diagnosis

Triple receptors-negative breast carcinoma, basal subtype

URL:	https://www.eurorad.org/case/8532
DOI:	10.1594/EURORAD/CASE.8532
ISSN:	1563-4086