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Metastatic breast carcinoma with mixed response to therapy
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An 83-year-old female with a family history of breast cancer was diagnosed in 1992 with a right breast cancer that was hormone receptor-positive, infiltrating ductal carcinoma.
She underwent right mastectomy and was surgically stage I (T1N0M0). She went on to receive adjuvant tamoxifen therapy.
In 1997, she noticed a right chest wall nodule that was excised and found to be recurrent breast cancer. Her metastatic work-up was negative for any distant disease.
She received a course of local radiation treatment and was subsequently followed off any treatment.
She did well until July 2005, when she had been complaining of right-sided chest pain. Her initial work-up, including a chest X-ray, was negative.
She subsequently underwent a PET/CT scan that showed nodular pleural thickening throughout the right lung that was hypermetabolic with standard uptake value (SUV) up to 3.0. There also was a 3-cm pleural-based mass in the right upper lobe that was hypermetabolic (SUV 8.4), consistent with metastatic disease.
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There was no evidence of any other sites of metastatic disease.
She was started on anastrozole and subsequent imaging showed a remarkable response.
She did well until October 2009. Repeat chest imaging showed mild progression of her pleural nodules, though she remained clinically asymptomatic.
She was switched to letrozole and, again, her disease remained stable for more than a year.
Around January of this year, she complained of significant shortness of breath with exertion. A repeat PET/CT scan showed progression of right pleural disease along with a large right pleural effusion.
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She underwent therapeutic thoracentesis with pleural fluid cytology positive for malignant cells, consistent with her primary breast cancer.
She was started on chemotherapy with carboplatin and gemcitabine. However, her clinical symptoms continued to worsen with increasing tumor markers.
Her chemotherapy was switched to vinorelbine in April, after which she had clinical improvement. Her most recent PET/CT scan in November showed improvement in her right pleural disease with a decrease in hypermetabolic activity. However, her liver showed new hypermetabolic foci with SUV ranging from 2.3 to 4.9, consistent with new metastatic disease.
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Images: M. Ghesani, MD |
Discussion
Breast cancer is the most common cancer in females and the second most common cause of cancer-related mortality in the United States.
Although a small subset of patients with low-volume metastatic disease could be managed with locoregional therapies — including surgery and radiation — most patients require systemic therapy in the form of hormonal therapy, or chemotherapy with or without biological therapy.
Breast cancer is a heterogeneous disease with several biological subtypes. Besides histology, grade and presence of hormonal receptors, newer techniques such as molecular profiling and gene expression profiling are increasingly being used to identify different subtypes of breast cancer.
These subtypes have shown to have both prognostic and predictive importance.
For example, a commercially available gene signature, Oncotype DX, now is included in the current National Comprehensive Cancer Network guidelines in management of node-negative, ER-positive breast cancers.
The patients in the low-risk group did not derive any benefit from adjuvant chemotherapy, as shown in patients treated in the NSABP B-20 study.
Similarly, molecular profiling has identified several distinct breast cancer subtypes. These include three subtypes of ER-negative tumors — HER-2–enriched, basal-like and normal-like — and two subtypes of ER-positive tumors, luminal A and luminal B.
Prat and colleagues recently described a claudin-low subtype that showed high levels of epithelial-mesenchymal transition genes and cancer stem cell-like features.
In addition, the hormone status and HER-2 receptor status can change over time as a result of evolution of tumor cells.
As presented by Locatelli and colleagues at ASCO 2010, there was discordance in hormone receptor status between the primary tumor and subsequent liver metastases in a review of 255 patients.
Overall, the ER status changed in 16%, PR status changed in 30% and HER-2 status changed in 13% of patients. Thus, it may be important to biopsy the site of metastatic disease, as it can result in a change in treatment.
As seen in our patient, she initially had hormone receptor-positive disease that did respond to hormonal therapy. She subsequently progressed and was started on systemic chemotherapy. However, although she had clinical and radiological improvement in her thoracic metastases, she was found to have progressive disease in her liver.
It is possible that her cancer cells have evolved into different biologic subtypes, each with different treatment response profiles. It may become important to better characterize these lesions, especially with advances in gene profiling, so a personalized therapeutic approach could be planned.
Munir Ghesani, MD, is an attending radiologist at St. Luke’s-Roosevelt Hospital Center and Beth Israel Medical Center and a HemOnc Today section editor. He is an associate clinical professor of radiology at Columbia University College of Physicians and Surgeons. Sumit Talwar, MD, is a fellow in hematology/oncology at St. Luke’s-Roosevelt Hospital Center. Eaton Lin, MD, is a resident in radiology at St Luke’s-Roosevelt Hospital Center. Gabriel Sara, MD, is an attending in hematology/oncology at St Luke’s-Roosevelt Hospital Center. Disclosures: Drs. Ghesani, Talwar, Lin and Sara report no relevant financial disclosures.
For more information:
- Fisher B. J Natl Cancer Inst Monogr. 2001; 30:62-66.
- Locatelli MA. J Clin Oncol. 2010; 28:18s. (suppl; abstr CRA1008).
- Prat A. Breast Cancer Res. 2010;12:R68.