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"Medical Journeys" is a set of clinical resources reviewed by doctors, meant for physicians and other healthcare professionals as well as the patients they serve. Each episode of this journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

This installment: A noteworthy case study.

What are the recommended next steps for this 68-year-old woman who discovered a lump in her left breast when she was referred by her family physician for imaging? That's what Kumaraman Srivastava of Anne Burnett Marion School of Medicine at Texas Christian University in Fort Worth, and colleagues set out to determine.

As they explained in the, the patient had no noteworthy medical history nor had she received routine breast screenings or breast biopsies. When she presented for assessment, she explained that for the last 9 months, she had become increasingly concerned when a new bluish/purple discoloration developed over the lump.

The imaging showed numerous abnormalities in the left breast and armpit, including a 4.6-cm irregular mass at 11 o'clock; a suspicious, enlarged axillary lymph node; and an area of 2.5 cm of heterogeneous calcifications in the 3 o'clock position.

The patient was given a mammography assessment, categorized as Breast Imaging-Reporting and Data System 5. Investigations included ultrasound-guided core needle biopsies of the two lesions located at 11:00 and in the axillary lymph node. Clinicians also performed a stereotactic core needle biopsy of the 3:00 calcifications.

The 4.6-cm lesion was found to be a grade 3 infiltrating ductal carcinoma with a minor squamous component. It was estrogen receptor (ER)+ (100%), progesterone receptor (PR)+ (100%), HER2/neu negative on fluorescence in situ hybridization (FISH). The Ki-67 score was 95%, and p53 was 100%.

Analysis of the sample from the lymph node identified metastatic breast carcinoma. Although this was primarily keratinizing squamous cell type, some of the tissue sample was similar to that of the breast tumor. "The node was ER 5%, PR-, and HER2/neu negative on FISH. Ki-67 was 80%, and p53 was 95. Biopsy of the calcifications revealed a small ductal carcinoma in situ.

Clinicians did not make any predictions about outcome at that time.

The team proposed a modified radical mastectomy of the left breast, with or without chemotherapy. Because her cancer was fairly extensive, the patient opted to receive neoadjuvant chemotherapy (NAC). Prior to that, she underwent staging scans, which showed no evidence of distant metastasis.

One month after her diagnosis, the patient started a regimen of doxorubicin and cyclophosphamide, which she received every 14 days for four cycles, followed by weekly treatment with paclitaxel for 12 cycles. She received her last round of chemotherapy 5 months after beginning treatment.

Clinicians monitored the patient's response to treatment with regular physical examinations. When the first cycle of chemotherapy had been completed, the primary tumor and lymph node had both decreased in size.

After the chemotherapy was completed, the patient had a final physical exam and diagnostic imaging of the breast and axilla. The results were positive, with indications that she had a complete pathologic response.

This meant, they said, that she was a candidate for a left localized partial mastectomy at the 12:00 and 3:00 positions with targeted axillary lymph node dissection. On the day before surgery, the team placed wireless localization reflectors at both breast sites and the clipped node. Surgery was performed successfully, and there were no complications.

During the surgery, the team performed a frozen section examination of four sentinel lymph nodes, including the prior biopsied node. Microscopic analysis showed no evidence of metastatic disease. Specimen x-rays taken during the surgery showed two partial mastectomy specimens with biopsy clips centered and reflectors in place.

Final testing of the sentinel lymph nodes showed a residual 8 mm invasive ductal carcinoma with negative margins at the 11:00 position. Tests of the four lymph nodes were negative, and the second sentinel lymph node showed the biopsy clip and evidence of scarring.

Pathologic analysis of the nodes at the 3 o'clock position found no evidence of residual carcinoma. Lobular carcinoma in situ was noted with all negative margins, and the patient's final pathologic stage was ypT1bypN0/stage IA breast carcinoma. The patient finished adjunct radiation treatment and continues to take antiestrogen therapy, the team reported.

Discussion

Metaplastic breast carcinoma () is a heterogeneous group of malignancies characterized by a non-glandular differentiation of breast tissue, including osseous, sarcomatous, and squamous histology, the case authors explained.

Under the World Health Organization classification of breast tumors, MpBC may be divided variously as epithelial, sarcomatoid, or mixed metaplastic. It typically presents as a triple-negative cancer, and tends to be larger and higher grade. Thus, compared with other triple-negative breast cancers, MpBC tends to have a worse prognosis -- likely related to its biology and generally poor response to chemotherapy.

MpBC is one of a rare group of malignancies, accounting for just 0.2-5% of breast cancers. Hence, data on MpBC are scarce, and currently limited to case reports, case series, and retrospective analyses. In the absence of consensus-based guidance on treatment, "physicians rely on case reports to help guide their understanding to help formulate optimal treatment options for patients," the authors stated.

Despite reports of some degree of response among some patients with MpBC, NAC remains largely in many patients, and their disease progresses.

"Due to the low reported response to NAC, and possible disease progression, treatment recommendations include early surgical resection and adjuvant therapy -- except in tumors <0.5 cm in size with no nodal or metastatic disease," Srivastava and co-authors noted.

Since these tumors are typically diagnosed at a later stage, when they tend to be large and high-grade, mastectomy is often necessary; surgery may be accompanied by adjuvant radiation, which has demonstrated survival benefits in these patients.

While chemotherapy also improves survival, its optimal role in treatment of patients who can undergo surgery is a subject of debate. And there is a lack of research data comparing adjuvant chemotherapy with NAC.

Complete pathological response to NAC is relatively rare in this cancer, the case authors noted. The positive outcome reported in their patient's case reflects the limited experience in this setting, which suggests similar overall with neoadjuvant and adjuvant chemotherapy in patients with node-positive disease.

Although MpBC is less likely than other breast cancers to respond to neoadjuvant treatment, patients who do receive to NAC have a higher of response or disease stability versus progression, Srivastava and co-authors noted.

Presurgical NAC has the potential to shrink the tumor, thus potentially reducing the extent of surgery required. Furthermore, data show similar outcomes with a conservative surgical approach compared with mastectomy, the team explained. "Additionally, NAC allows for in-vivo chemo-responsiveness to aid in adjuvant therapy planning and potential nodal regression, thus avoiding complete axillary node dissection."

That NAC was associated with a close to complete response in this patient's node-positive MpBC highlights the potential benefit of starting such patients on this treatment, the team concluded. Compared with initiating surgical treatment early, as recommended, starting NAC "could allow for decreased morbidity without increased mortality."

Read previous installments in this series:

Part 1: Breast Cancer -- The Basics of Diagnosis, Staging, and Treatment

Part 2: Breast Cancer: Making the Diagnosis With Breast Biopsy

Part 3: What to Know About Management of Early-Stage Breast Cancer

Part 4: New Treatment Options for Locally Advanced and Metastatic Breast Cancer

Part 5: Genetic Testing in Breast Cancer: Mutations, Multigene Panels, and More

Part 6: Case Study: Older Male With Rash, Chest Swelling, and Mysterious Skin Issues

Part 7: Breast Cancer Palliative Care and Metastatic Disease: Looking Beyond End of Life

Part 8: Breast Cancer and Post-Surgical Screening: Advising Patients on Appropriate Imaging

Part 9: The Key Role of Primary Care Providers in Managing Breast Cancer Tx-Related AEs