|Year : 2016 | Volume
| Issue : 4 | Page : 115-117
Management of triple-negative invasive ductal cell carcinoma
Zil-e-Ali Ahsan1, Assad Salman1, Thomas Nicholas Todd2
1 Department of Surgical Oncology, ARH Medical Centre, Hazard, Kentucky, USA
2 Department of General Surgery, ARH Medical Centre, Hazard, Kentucky, USA
|Date of Submission||11-Aug-2016|
|Date of Acceptance||23-Nov-2016|
|Date of Web Publication||3-Jan-2017|
Department of Surgical Oncology, ARH Medical Centre, Hazard, Kentucky
Source of Support: None, Conflict of Interest: None
We reported a case of triple-negative breast cancer who presented to our medical center with a mass in the upper outer quadrant of the left breast. The age of the patient at the time of presentation was 74 years and 8 months. Breast ultrasound revealed a 3.3 cm × 2.7 cm lobulated hypoechoic fibroglandular mass in the upper outer quadrant of the left breast. Core biopsy showed triple-negative (estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2/neu negative) invasive ductal cell cancer of the left breast infiltrating into the skin but no fixation to the chest wall. Neoadjuvant chemotherapy reduced the size of the mass to 2.1 cm × 1.2 cm. Partial mastectomy was then performed along with partial axillary dissection and adjuvant radiotherapy. No recurrence of tumor or any recent breast mass was noted at 1-year follow-up on both mammography and ultrasonography, indicating successful management of triple-negative breast tumor. We conclude that triple-negative breast tumors should be managed with neoadjuvant chemotherapy such as taxanes and cisplatins followed by adjuvant radiotherapy.
Keywords: Chemotherapy, invasive ductal cell carcinoma, partial mastectomy, radiotherapy, triple-negative breast cancer
|How to cite this article:|
Ahsan Ze, Salman A, Todd TN. Management of triple-negative invasive ductal cell carcinoma. Transl Surg 2016;1:115-7
| Introduction|| |
Breast cancer is a heterogeneous disease that encompasses several distinct molecular profiles with different clinical behaviors and responses to therapy. Here, we report the management of a rare case of triple-negative breast cancer (TNBC) with surgery and cytotoxic chemotherapy followed by adjuvant radiotherapy. Tumor size, lymph node status, and grade in conjunction with standardized immunohistochemical assessment of hormone receptors (i.e., estrogen receptor [ER], progesterone receptor [PR]) and human epidermal growth factor receptor 2 (HER2) are currently used in the management of breast cancer patients. Regional management of breast cancer has been used based on the results of randomized controlled trials comparing breast-conserving therapy (i.e., lumpectomy and adjuvant radiation therapy) and modified radical mastectomy. ,, However, among those studies, molecular and biologic heterogeneity of breast cancer outcome was not considered. Indeed, over the past decade, four major molecular subtypes have been introduced through genomic and molecular profiling associated with differences in survival rates and responses to treatment. ,, Most studies have focused on biologic subtyping using ER, PR, and HER2 as biomarkers to approximate these molecular subtypes. , TNBCs present poorly differentiated tumors which are characterized by high proliferation rate and increased aggressiveness compared with other subtypes. ,,, TNBCs are not benefited from hormonal or trastuzumab-based therapies because of the absence of target receptors such as ER, PR, and HER2. Hence, conventional cytotoxic chemotherapy followed by adjuvant radiotherapy is the standard of care for these patients. The paucity of therapeutic options emphasizes the urgent need to optimize the current management of patients with TNBC and reduce their risk of locoregional recurrence.
| Case Report|| |
A female patient aged 74 years and 8 months presented to the hospital with a mass, measuring 3.3 cm × 2.7 cm, on the upper outer quadrant of the left breast, measured from the nipple laterally and including the central portion of the breast. Infiltration into the skin was observed with no fixation to the chest wall. Breast ultrasound done showed 3.3 cm × 2.7 cm lobulated hypoechoic mass, and core biopsy showed invasive ductal cell cancer of the left breast. Case history showed a diagnosis of actinic keratosis on both cheeks of face, for which she was prescribed topical fluorouracil and advised to use moisturizers. She is a known hypertensive patient and on antihypertensives for 25 years. She is alcoholic and smoker and her counseling to quit smoking and alcohol consumption was done accordingly. Family history showed colorectal cancer in three family members and breast cancer in a paternal aunt. The histopathologic findings of the core needle biopsy showed invasive ductal cell carcinoma, ER-negative, PR-negative, and HER2-neu-negative or triple-negative tumor. Immunohistochemical examination and/or fluorescence in situ hybridization (FISH) was used to determine ER, PR, and HER2-neu status. ER and PR results were considered positive with ≥1% positively staining cells. HER2-neu was considered positive with either 3+ immunoreactivity or amplification by FISH. The patient was on triamterene-HCTZ (50-75 mg), simvastatin (20 mg), and ranitidine HCL 150 mg, with known allergies to acetaminophen and loratadine. Mammogram done 6 months after breast cancer diagnosed and treated with neoadjuvant chemotherapy showed no calcifications with the Breast Imaging Reporting and Data System 1. Ultrasound showed fibroglandular tissue in the upper outer quadrant of the left breast showing complex nodule, with central cystic area measuring about 2.1 cm × 1.2 cm and a cluster of small cysts within. Another well-circumscribed small nodule showing posterior shadowing representing area of calcification was observed.
Partial mastectomy procedure was then performed which involved placing a crescent and batwing incision and elevating superior and inferior flaps around the area of the lesion which was localized sonographically on the previous day. The specimen was then taken to a back table where the margins were painted with Vector kit and then the radiopaque markers were placed on the margins. It was then taken to the radiology department where specimen radiograph was obtained showing a good acquisition of three clips that had been placed preoperatively, one each at the upper and lower edges of the tumor and one in the center. The wound was then closed after elevating the breast tissue off the chest wall and closing the lumpectomy site with 3-0 Vicryl suture in layers. A clip was placed at the center of the tumor. The skin was closed with 3-0 Vicryl followed by 2-0 Quill. Three-dimensional conformal accelerated partial breast irradiation was used for postmastectomy radiotherapy to the left breast. No recurrence of tumor or any recent breast mass was noted at 1-year follow-up on both mammography and ultrasonography, indicating the successful management of triple-negative breast tumor.
| Discussion|| |
Patients with TNBC are not benefited from hormonal or trastuzumab-based therapies because of the absence of target receptors such as ER, PR, and HER2. Hence, the available treatment options are surgery, chemotherapy, and radiotherapy, individually or in combination. New targeted therapeutic drugs against cell surface receptors such as epidermal growth factor receptor (EGFR) and c-Kit are currently under consideration. Livasy CA et al.  reported the presence of c-Kit in 31% of basal-like tumor cells and 11% of nonbasal-like tumor cells. Our patient had BRCA1-deficient triple-negative tumor. Some recent reports suggest that because BRCA1-deficient breast tumors share the characteristics of basal-like tumors, the therapeutic management that targets basal-like tumors should also be highly effective in the treatment of BRCA1-deficient breast cancer and triple-negative tumors. 
Genomic instability and predisposition to carcinogenesis due to mutations in the BRCA1 gene are the consequences of defects in DNA repair. This process could be related to the control of proliferation in BRCA1-related, triple-negative, and basal-like tumor cells. Results from several in vitro studies have shown that breast tumor cells with BRCA1 mutations are extremely sensitive to drugs that induce cross-links (mitomycin-C and platinum) and single- and double-strand breaks (etoposide and bleomycin) in DNA. , Base-excision repair pathways with poly ADP-ribose polymerase 1 (PARP1) enzyme are used in single-strand DNA breaks. Cells without BRCA1 were shown to be incapable of repairing DNA strand breaks, and apoptotic processes were enhanced by the inhibition of PARP1. ,, Hence, BRCA1 null cells were shown to be more sensitive to chemo- and radio-therapies. In contrast, these cells were shown to be resistant to mitotic-spindle targeting drugs such as taxanes and vinorelbine.  Targeted therapy can be used to dysfunction BRCA1 and PARP1 pathways in a significant subgroup of triple-negative and basal-like breast tumors. , In addition, local radiotherapy may be of significant benefit for patients with triple-negative cancer because ionizing radiations also provoke DNA strand breaks. Drugs such as carboplatin, cisplatin, PARP1 inhibitors, and docetaxel could be valuable in the treatment of patients with advanced triple-negative cancers. Approximately, 66% of breast cancer patients with triple-negative and basal-like tumor cells have been reported to express EGFR. ,, Inhibition of EGFR might be an useful therapeutic strategy. Clinical trials evaluating the efficacy of humanized anti-EGFR monoclonal antibodies and EGFR tyrosine kinase inhibitors in patients with TNBC are currently under way. 
It is instrumental to determine the ER, PR, and HER2 status for TNBC diagnosis; therefore, it will be plausible to demonstrate the immunohistochemistry results of ER, PR, and HER2 as well as the HER2 FISH result. Given that the patient has a family history and BRCA screening has been performed, presenting the screening result will be required if further treatment based on BRCA status is proposed. The mammography and ultrasonography performed before treatment and at 1-year follow-up shows the successful management of this case.
In conclusion, neoadjuvant cytotoxic chemotherapy followed by adjuvant radiotherapy is the standard of care for patients with TNBCs since endocrine and HER2-targeted therapies cannot be offered. We conclude that the triple-negative breast tumors should be managed with neoadjuvant chemotherapy, with drugs such as taxanes, cisplatins, and carboplatins followed by surgery and adjuvant radiotherapy as it is clear that the targeted therapy has no role.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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