Course Authors
Robert G. Lerner, M.D.
In the past three years, Dr. Lerner has served as a consultant for RPR, and has served on the Speakers' Bureau for Pharmacia & Upjohn.
Estimated course time: 1 hour(s).
Albert Einstein College of Medicine – Montefiore Medical Center designates this enduring material activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
In support of improving patient care, this activity has been planned and implemented by Albert Einstein College of Medicine-Montefiore Medical Center and InterMDnet. Albert Einstein College of Medicine – Montefiore Medical Center is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.
Upon completion of this Cyberounds®, you should be able to:
Describe the clinicopathologic entity of inflammatory breast cancer
Discuss the prognosis for women with inflammatory breast cancer
Explain the dramatic improvement in prognosis since the introduction of modern combined modality therapy
Discuss the availability of and controversy surrounding the use of autologous bone marrow transplantation for breast cancer.
The Case
A 46-year-old woman noted an enlarging mass in her right breast in January 1991. A biopsy in May 1991 was read as invasive ductal cancer with inflammatory features. Because of the aggressive nature of any breast cancer with inflammatory features her physician referred the patient for aggressive, combined, modality treatment, including bone marrow transplantation as initial therapy. After we explained the aggressive nature of this tumor and potential benefits of combined modality treatment, the patient was enrolled into a program.
The plan for this patient included intensive neoadjuvant chemotherapy followed by radiotherapy and surgery and, then, high dose chemotherapy with autologous bone marrow transplantation (BMT) for restoration of bone marrow function after the chemotherapy. Neoadjuvant chemotherapy is chemotherapy given before anticipated surgery in an attempt to shrink the cancer so that it can be more easily removed by surgery. This was carried out by treating her with 5- flurouracil, doxorubicin and cyclophosphamide chemotherapy for four cycles from May to August 1991.
The chemotherapy resulted in a partial response that allowed the cancer to be resected. She then underwent a right modified radical mastectomy in September 1991. This patient's high dose chemotherapy consisted of thiotepa, mitoxantrone and carboplatin. Immediately prior to the high dose chemotherapy in December 1991, her bone marrow was harvested and returned to her by infusion after the chemotherapy to restore bone marrow function. This autologous bone marrow transplant engrafted well, restoring her blood counts in two weeks.
She then received adjuvant radiation therapy to the chest wall in early 1992 to prevent any local recurrence. This concluded her combined modality therapy for inflammatory breast cancer. She has been under a close follow-up by her oncologist since then. She continues to have no evidence of disease clinically, as well as by mammograms, CT Scans and tumor markers such as CA 15-3. Her last follow-up was in January 1999 with no evidence of disease and normal activity.
Discussion
Breast cancer is the most frequently diagnosed cancer in American women and the second most frequent cause of cancer death.(1) Over the past several decades, there has been a fairly steady and large increase in the incidence of the disease. Data collected between 1988 and 1990 indicate that the lifetime risk of developing breast cancer is 12.2%, or 1 in 8 women.(2) Currently, about half of patients given the diagnosis of breast cancer can be expected to live out the rest of their lives without recurrence, though one-third will die of their disease. However, late recurrences occur and there is no time at which patients can be completely assured that the disease will not recur.(3) Among the various subgroups, inflammatory breast cancer (IBC) carries the most ominous prognosis, although the outlook is changing considerably with the advent of better neoadjuvant chemotherapy.(4)
Clinicopathology
IBC is a distinct clinicopathologic entity, characterized clinically by the presence of diffuse brawny edema of the skin of the breast with an erysipiloid edge, usually without an underlying palpable mass. This clinical presentation is due to the defining pathologic finding of tumor embolization of dermal lymphatics. IBC is the most aggressive breast neoplasm and, fortunately, uncommon in the United States. Nearly all patients with IBC are dead within five years in the absence of systemic therapy. Historically, results of surgical treatment were very poor with a high local recurrence rate and difficulty in obtaining clear margins.(5) Radiation alone was ineffective and a series published from the Massachusetts General Hospital reported a 69 % local and regional recurrence rate.(6)
Treatment
Preoperative chemotherapy of patients with IBC produces a response rate of about 80%, and most patients can go on to surgical resection with clear margins. As in other patients with locally advanced breast cancer, the most typical approach is to use an anthracycline and/or taxane based chemotherapy combination as induction, followed by surgery, then additional chemotherapy and, finally, consolidation radiation therapy. With this type of combined modality approach, about 70% of patients achieve local tumor control. This is especially true of patients whose tumors respond well to initial chemotherapy.
Prognosis
Patients with IBC who successfully complete a combined modality therapy have a prognosis that is dramatically improved when compared to the era prior to the use of combined chemotherapy. About 50% of patients treated with combined modality treatment survive for five years, and about 35 % of the patients are reported to be disease-free at 10 years.(7)
Reflecting back on the case just described, you can now appreciate that what at first appeared to be a startlingly good result attributable to the use of high dose chemotherapy with autologous BMT to restore bone marrow function might have been achieved without autologous BMT. There are several reports of non-randomized retrospective analysis of the survival of patients with IBC after autologous BMT.(8),(9),(10) Recent reports of still ongoing large cooperative trials, comparing modern chemotherapy of breast cancer to more intensive therapy with autologous BMT, have so far failed to show a benefit. The National Cancer Institute press release dealing with this new information has been posted on the web:
One smaller randomized trial had suggested a benefit to adding BMT to standard therapy for metastatic breast cancer but did not address inflammatory breast cancer.(11) Upon further review, the results of the trial were found to be fraudulent(12) and subsequent clinical trials have not yet supported the use of high-dose chemotherapy as the standard of care.