Exploring neoadjuvant chemotherapy in a rare case of male breast cancer—a TEC-regimen (docetaxel, epirubicin, and cyclophosphamide) treatment: a case report and literature review

Introduction

Male breast cancer (MBC) is an uncommon but clinically challenging malignancy, accounting for only 0.5–1% of all breast cancer cases worldwide (1). Due to its rarity and the consequent paucity of large-scale studies, current diagnostic and therapeutic strategies for MBC are largely extrapolated from evidence derived in female breast cancer populations.

At presentation, MBC is frequently diagnosed at a locally advanced stage, often characterized by larger tumor volume, skin involvement, and infiltration of the pectoralis muscle or axillary lymph nodes (2). These features increase surgical complexity and limit opportunities for conservative surgery or aesthetic reconstruction. In contrast, NAC has been widely established in female breast cancer, where it can effectively downstage disease, increase breast-conserving surgery rates, and provide an in vivo assessment of chemosensitivity. However, NAC remains underutilized in MBC, and data on its efficacy in male patients are scarce (3).

A Swedish retrospective cohort study demonstrated that the proportion of male patients receiving NAC was comparable to that of female patients, but the rate of pathological complete response (pCR) in men, although lower, did not reach statistical significance. These findings suggest that NAC can be a viable option for tumor downstaging in MBC, particularly in locally advanced or large-volume tumors, potentially improving operability and facilitating reconstructive procedures.

In the absence of robust prospective data guiding systemic therapy sequencing in MBC, treatment strategies are frequently extrapolated from female breast cancer paradigms. In this context, NAC represents a rational approach for selected patients with locally advanced disease, aiming to achieve tumor downstaging and improve surgical feasibility (4).

Here, we report a representative case of a large, HER2-negative, Luminal B-type male breast carcinoma treated with six cycles of TEC (docetaxel, epirubicin, and cyclophosphamide) NAC, followed by radical resection and flap reconstruction. This case highlights the clinical feasibility and potential benefits of NAC in locally advanced MBC and is accompanied by a review of the literature to contextualize its therapeutic implications for surgical planning and adjuvant management. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-305/rc).

Case presentation

A 54-year-old man presented with a palpable mass in the right breast that had been present for three years and had recently enlarged over the preceding month. He was otherwise healthy, with no history of hypertension, diabetes, or other chronic illnesses, and denied smoking, alcohol use, or a family history of breast or ovarian cancer. Physical examination revealed a firm, irregular mass measuring approximately 6.0 cm × 5.0 cm in the upper inner quadrant of the right breast, with indistinct borders and overlying skin ulceration. A hard, immobile lymph node approximately 1.0 cm in diameter was palpable in the right axilla, while the contralateral breast and axilla appeared normal (Figure 1).

Figure 1 Clinical appearance of the right breast showing a palpable mass with overlying skin ulceration, vascular congestion, and inflammatory edema (area highlighted in red), indicating cutaneous involvement. This image is published with the patient’s consent.

Ultrasonography demonstrated an irregular hypoechoic lesion in the upper inner quadrant of the right breast measuring 5.6 cm × 5.8 cm × 4.1 cm, with poorly defined margins and abundant internal vascularity [Breast Imaging Reporting and Data System (BI-RADS) category 5]. The right axillary lymph nodes showed cortical thickening (Figure 2). Staging evaluation with brain magnetic resonance imaging, thoraco-abdominal computed tomography (CT), and whole-body positron emission tomography-computed tomography (PET-CT) revealed no evidence of distant metastasis.

Figure 2 Ultrasonographic image revealing an irregular hypoechoic mass with ill-defined margins and abundant internal vascular flow, suggestive of rich tumor vascularization and invasive potential.

Core-needle biopsy confirmed invasive ductal carcinoma of no special type (NST), histologic grade II (6 points). Immunohistochemistry (IHC) revealed strong positivity for estrogen receptor (ER ≈90%, 3+), progesterone receptor (PR ≈90%, 3+), and androgen receptor (AR ≈80%, 3+), with HER2 negativity (0) and a Ki-67 proliferation index of approximately 20%. Cytologic examination of the axillary lymph node aspirate showed malignant cells (Figures 3,4). On the basis of clinical and radiological findings, the tumor was staged as cT4N1M0, stage IIIB, Luminal B1 subtype (luminal subtype classification was defined according to the St. Gallen International Expert Consensus criteria).

Figure 3 Hematoxylin and eosin staining demonstrating invasive ductal carcinoma of no special type (magnification, 100×). The tumor cells form irregular glandular structures accompanied by stromal desmoplastic reaction.

Figure 4 Cytological smear showing clustered adenocarcinoma cells with enlarged nuclei, hyperchromatic chromatin, and prominent nucleoli—features consistent with a diagnosis of ductal carcinoma (Papanicolaou staining; magnification, 400×).

The patient underwent NAC with the TEC regimen—NAC was administered using the TEC regimen, consisting of docetaxel 75 mg/m² (actual dose 120 mg), epirubicin 75 mg/m² (actual dose 120 mg), and cyclophosphamide 500 mg/m² (actual dose 800 mg), given every 3 weeks for a total of six cycles. No prophylactic granulocyte colony-stimulating factor support was administered. The patient completed all six cycles without dose reduction or treatment interruption and tolerated chemotherapy well, with no grade ≥3 adverse events observed. Follow-up CT imaging revealed reduction of the primary tumor to approximately 4.8 cm × 2.2 cm × 5.0 cm, decreased enhancement, and regression of axillary lymphadenopathy, consistent with a partial response (PR). Although breast ultrasound was used for initial diagnosis, contrast-enhanced CT was selected for response assessment to ensure consistency with systemic staging and to allow reproducible measurement of tumor size together with evaluation of intrathoracic structures. Subsequently, he underwent right modified radical mastectomy with axillary lymph-node dissection and reconstruction using a latissimus dorsi myocutaneous flap, with intraoperative indocyanine-green fluorescence angiography used to assess flap perfusion.

Postoperative histopathology demonstrated residual invasive ductal carcinoma with a maximal diameter of approximately 5.0 cm and evidence of chemotherapy-induced fibrosis and necrosis. The Miller-Payne grading system classifies pathological response into five grades based on the reduction in tumor cellularity. A grade 2 response corresponds to a ≤30% reduction in tumor cellularity, consistent with the observed histopathological findings in this case. Examination of lymph nodes showed no metastases in level I (0/11), level II (0/1), or interpectoral nodes (0/2); however, one internal mammary lymph node was positive for metastasis. A discrepancy in HER2 immunohistochemical results was observed between the core needle biopsy (HER2 0) and the surgical specimen (HER2 2+). This inconsistency was interpreted as intratumoral heterogeneity and sampling variability, which have been reported in breast cancer. Subsequent fluorescence in situ hybridization (FISH) analysis demonstrated no HER2 gene amplification, and the tumor was therefore classified as HER2-negative. The final pathologic stage was yPT2N1bMx. The internal mammary lymph node metastasis was not detected on baseline PET-CT, which may reflect subclinical disease below the detection threshold or a discordant nodal response to NAC rather than true interval progression, as no treatment delay occurred.

Genomic profiling assays, such as Oncotype DX, were not performed in this patient. This decision was based on the limited clinical utility of genomic risk stratification after completion of NAC, as well as the fact that the patient had already received a full course of systemic therapy. Considering the absence of distant metastasis and the planned adjuvant radiotherapy and endocrine therapy, no additional adjuvant chemotherapy was administered. Adjuvant radiotherapy was delivered to the chest wall and regional lymphatic drainage areas using intensity-modulated radiotherapy, with a total dose of 50 Gy in 25 fractions. Tamoxifen was initiated postoperatively with an intended duration of 5 years. The patient tolerated endocrine therapy well without notable adverse effects. At the most recent follow-up, 12 months after surgery, no evidence of local recurrence or distant metastasis was observed. At the most recent follow-up, he remained in good general condition, with well-healed surgical wounds and no evidence of local recurrence or distant metastasis.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

This case describes a rare instance of MBC of the Luminal B1 subtype, characterized by a large primary tumor (clinical T4) with overlying skin ulceration, axillary nodal involvement, and high expression of ER, PR, and AR, but negative HER2 status and an intermediate Ki-67 index. Following six cycles of TEC-based NAC (anthracycline + taxane + cyclophosphamide), the patient achieved partial radiologic response, and postoperative pathology confirmed a stage of yPT2N1bMx with a Miller-Payne grade 2 histologic response. All surgical margins were negative, though one internal mammary lymph node showed metastatic involvement. Adjuvant radiotherapy and tamoxifen endocrine therapy were subsequently administered.

To date, reports of MBC cases undergoing a sequential multimodal treatment approach—comprising NAC, radical surgery with reconstruction, adjuvant therapy, and documented follow-up—remain exceedingly rare. Only three previously published cases have described this sequence in part or in near completeness, but none have simultaneously detailed all elements, including a clearly defined NAC regimen, reconstructive procedure, adjuvant therapy, and outcome data. The present report thus represents one of the few, and perhaps the most complete, accounts of such an integrated therapeutic approach—approximately the fourth case of its kind in the existing literature.

This case underscores both the clinical feasibility and potential value of NAC in selected patients with locally advanced MBC, particularly those with hormone receptor-positive, HER2-negative tumors amenable to subsequent endocrine therapy. Moreover, the successful implementation of reconstructive surgery following NAC illustrates that, with appropriate patient selection and multidisciplinary coordination, oncologic control and postoperative function can be achieved without compromising safety. A literature review was conducted using PubMed and Web of Science with the search terms “male breast cancer” and “NAC”, yielding 27 articles, of which 3 case reports met the inclusion criteria (Table 1).

Efficacy of NAC and the probability of pCR in MBC

According to data from a Swedish nationwide cohort, the utilization rate of NAC does not differ significantly between men and women with early-stage or locally advanced breast cancer. Although the proportion of male patients receiving NAC was slightly lower, the difference was not statistically meaningful. Among those treated, the rate of pCR was 16.7% in men compared with approximately 21.2% in women. More detailed analyses revealed that pCR rates in MBC were consistently lower than in female counterparts, particularly within the HR⁺/HER2⁻ and HR⁺/HER2⁺ subtypes. Nevertheless, the prognostic association between pCR and overall survival (OS) was also confirmed in men, underscoring its relevance across sexes (4).

Alternative neoadjuvant strategies, including endocrine therapy and emerging immunotherapy approaches, have also been explored in hormone receptor-positive breast cancer. Recent trials such as KEYNOTE-756 and CheckMate-7FL are investigating the role of immunotherapy in this setting; however, evidence in MBC remains limited.

Although the present case did not achieve pCR, PR and radiologic downstaging were attained—findings that mirror the prevailing trend in published MBC reports, where complete eradication of disease is rare but NAC frequently improves resectability and facilitates curative surgery.

Predictive and prognostic role of AR expression in NAC

In a retrospective analysis from Tianjin Medical University Cancer Institute and Hospital involving 1,231 women with breast cancer who received NAC, the expression of AR was commonly co-expressed with ER and PR across multiple molecular subtypes. However, no significant correlation was found between AR positivity and pCR rate (8). Similarly, a study from Nanjing (9) demonstrated that high AR expression was significantly associated with ER/PR positivity, molecular subtype, and Ki-67 index, yet AR did not emerge as a strong independent predictor of pCR. Recent studies suggest that AR expression may influence prognosis and therapeutic response in hormone receptor–positive breast cancer. Emerging evidence also supports the potential role of AR-targeted therapies in selected patients, particularly in the metastatic setting (10).

The current patient, with a Luminal B1 phenotype characterized by high ER and PR expression, HER2 negativity, and strong AR positivity, exemplifies this biological profile. Previous studies have reported that AR is prevalent among hormone receptor–positive breast cancers, and some have linked AR expression to improved long-term prognosis, although its predictive value for chemotherapy response remains inconsistent. In HR⁺/HER2⁻ subtypes, AR-negative tumors have been shown to exhibit higher pCR rates, whereas AR-positive tumors tend to demonstrate better endocrine responsiveness and potentially lower recurrence risk. In this context, the high AR expression observed in the present case may align with both its luminal characteristics and its anticipated sensitivity to endocrine therapy, despite the absence of a complete pathological response.

Tumor downstaging and surgical feasibility following NAC

For patients with large, node-positive, or locally advanced MBC, NAC has been reported to induce substantial tumor downstaging, thereby improving the likelihood of complete resection. Although breast-conserving surgery is rarely pursued in men, preoperative chemotherapy can occasionally reduce tumor extent and enable smaller or more reconstructive-friendly surgical procedures. Given that most male patients present at an advanced stage with extensive disease, NAC remains a critical strategy to enhance surgical feasibility. In the present case, successful radical resection with flap reconstruction and clear surgical margins were achieved, consistent with prior evidence supporting the use of NAC to optimize resection boundaries and surgical outcomes (11).

Biomarkers predicting response to NAC

A recent study published in Diagnostic Pathology analyzed 189 patients who underwent NAC for breast cancer and assessed correlations between various biomarkers—including ER, PR, HER2, Ki-67, AR, and p53—and treatment response. The study identified HER2 positivity, low tumor burden, and higher Ki-67 indices as factors associated with higher pCR rates and greater tumor shrinkage. Although AR was included in the analysis, its role as an independent predictor of pCR was not conclusively established (12).

In this case, the relatively modest Ki-67 index (approximately 20%) and HER2 negativity may partly explain the absence of pCR, while the tumor’s large size and involvement of the skin and pectoralis muscle further contributed to the limited response. These observations highlight the multifactorial nature of NAC responsiveness in MBC and underscore the need for refined predictive models integrating hormonal, proliferative, and molecular markers.

Residual cancer burden (RCB) and long-term prognosis

Multiple studies—including a pooled analysis published in The Lancet Oncology—have demonstrated a strong correlation between RCB and long-term outcomes following NAC, with lower RCB scores consistently associated with improved disease-free survival (DFS) and OS (13). Although a pCR was not achieved in the present case, nor was RCB quantitatively assessed, the observed pathological downstaging, successful surgical resection with negative margins, and subsequent adjuvant radiotherapy and endocrine therapy are expected to substantially reduce residual tumor burden. Collectively, these factors may contribute to favorable long-term disease control and overall prognosis.

Conclusions

This case supports the application of NAC in selected MBC patients to achieve effective tumor downstaging, thereby enabling complete resection and optimizing outcomes when combined with surgery, radiotherapy, and endocrine therapy. High AR expression may serve as a potential indicator of endocrine sensitivity and favorable long-term prognosis; however, its predictive value for NAC response remains uncertain. Future case reports and cohort studies should emphasize detailed characterization of molecular subtypes, AR status, pathological response grading, and long-term survival data to refine therapeutic strategies and inform evidence-based guidelines for the management of MBC.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-305/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-305/prf

Funding: This work was supported by the Characteristic Innovation Project of Ordinary Universities in Guangdong Province, China entitled “Study on the Mechanism of Aryl Hydrocarbon Receptor (AhR) and Hypoxia Interaction Mediating Vasculogenic Mimicry in Breast Cancer” (No. 2021KTSCX037).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-305/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Bhardwaj PV, Gupta S, Elyash A, et al. Male Breast Cancer: a Review on Diagnosis, Treatment, and Survivorship. Curr Oncol Rep 2024;26:34-45. [Crossref] [PubMed]
2. Lin AP, Huang TW, Tam KW. Treatment of male breast cancer: meta-analysis of real-world evidence. Br J Surg 2021;108:1034-42. [Crossref] [PubMed]
3. Schiza A, Fredriksson I, Sund M, et al. Treatment utilization and effectiveness of neoadjuvant chemotherapy comparing men and women diagnosed with breast cancer: a Swedish retrospective cohort study. Breast Cancer Res Treat 2024;203:235-43. [Crossref] [PubMed]
4. Hassett MJ, Somerfield MR, Baker ER, et al. Management of Male Breast Cancer: ASCO Guideline. J Clin Oncol 2020;38:1849-63. [Crossref] [PubMed]
5. Banys-Paluchowski M, Burandt E, Banys J, et al. Male papillary breast cancer treated by wide resection and latissimus dorsi flap reconstruction: A case report and review of the literature. World J Clin Oncol 2016;7:420-4. [Crossref] [PubMed]
6. Choong WL, Pitsinis V. Neoadjuvant Chemotherapy for Male Breast Cancer - “Pushing the Boundaries”. Hellenic J Surg 2019;91:102-4.
7. Qiao W, Li P, Chang C, et al. Male breast cancer following complete remission of acute myeloid leukemia: A case report and literature review. Int J Surg Case Rep 2025;134:111726. [Crossref] [PubMed]
8. Shi Z, Liu Y, Zhang S, et al. Evaluation of predictive and prognostic value of androgen receptor expression in breast cancer subtypes treated with neoadjuvant chemotherapy. Discov Oncol 2023;14:49. [Crossref] [PubMed]
9. Wang DD, Jiang LH, Zhang J, et al. Androgen receptor expression and clinical characteristics in breast cancer. World J Surg Oncol 2024;22:243. [Crossref] [PubMed]
10. Guidi L, Trapani D, Curigliano G. Targeting androgen receptors in patients with metastatic breast cancer. Curr Opin Oncol 2025;37:562-9. [Crossref] [PubMed]
11. Lee EG, Lee DE, Kim HH, et al. Androgen Receptor as a Predictive Marker for Pathologic Complete Response in Hormone Receptor-Positive and HER-2-Negative Breast Cancer with Neoadjuvant Chemotherapy. Cancer Res Treat 2023;55:542-50. [Crossref] [PubMed]
12. Wang M, Wei Z, Kong J, et al. Comprehensive evaluation of the relationship between biomarker profiles and neoadjuvant chemotherapy outcomes for breast cancer patients. Diagn Pathol 2024;19:53. [Crossref] [PubMed]
13. Sanft T, Harrigan M, McGowan C, et al. Randomized Trial of Exercise and Nutrition on Chemotherapy Completion and Pathologic Complete Response in Women With Breast Cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis Study. J Clin Oncol 2023;41:5285-95. [Crossref] [PubMed]