Two years after her first mammogram the patient, EC, noticed swelling and skin changes in one breast. A bone scan, chest and abdomen CT, and PET scan were negative for metastatic spread, staging the cancer at IIIB.
IBC is an aggressive breast cancer, sometimes mistaken for contact dermatitis, in which many patients do not have a palpable mass. Management of this deadly disease is evolving.
The patient, EC, is a premenopausal 38-year-old mother of four school-age children. Her mother had been diagnosed and treated for breast cancer. Because of her family history of breast cancer, EC had her first mammogram at age 36. That first mammogram showed clustered calcifications and EC was told this was a warning sign. A biopsy was negative for cancer. In spite of the reassuring report, EC opted to return every 6 months for follow-up with her obstetrician-gynecologist.
EC received standard neoadjuvant doxorubicin and cyclophosphamide in a 3-week regimen for six cycles. This was followed by a modified radical mastectomy with axillary node dissection. Owing to evidence of residual disease, adjuvant chemotherapy (docetaxel) was given in a 3-week regimen for four cycles. Daily radiotherapy to the chest wall and axilla completed the treatment. EC was instructed to follow up with physical therapy to improve range of motion in the affected arm and told she could resume regular activities as tolerated.
Two years after that first mammogram, near when EC was due for her annual mammogram, she noticed swelling and skin changes in one breast. These worrisome symptoms sent her to her obstetrician-gynecologist ahead of schedule. Because of her history, EC was sent to a breast surgeon for evaluation. A biopsy of the breast tissue revealed inflammatory breast cancer (IBC). A bone scan, chest and abdomen CT, and PET scan were negative for metastatic spread, staging the cancer at IIIB.
EC had access to a large metropolitan cancer center with physicians who were familiar with inflammatory breast cancer. Testing indicated that the cancer was estrogen- and progesterone-receptor negative and did not overexpress HER2-neu. (This type of cancer is commonly referred to as triple-negative breast cancer.) Neoadjuvant chemotherapy consisting of doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) was given every 3 weeks for a total of six cycles. This was followed by a modified radical mastectomy and axillary node dissection.
Pathology results indicated residual disease in four axillary lymph nodes and breast tissue removed. After a 3-week surgical recovery period, adjuvant chemotherapy was started using docetaxel (Taxotere) on a 3-week schedule for four cycles. Daily radiotherapy to the axilla and chest wall for 6 weeks completed the course of treatment. CT and PET scans at the close of treatment revealed no evidence of active disease.
Typical appearance of inflammatory breast cancer. Photograph courtesy of Wendy A. Woodward, MD, PhD.
Inflammatory breast cancer is a clinicopathological entity characterized by diffuse erythema and edema (peau d’orange) of the breast, often without a palpable mass. It is described by the American Joint Committee on Cancer as a T4d tumor or IIIB. EC’s increase in breast size as well as changes to the texture and color of the skin are classic symptoms of inflammatory breast cancer (see Figure 1). Typically, imaging has not played a significant role in the diagnosis of IBC. Mammography and ultrasound seldom detect the subtle differences in breast texture or density. Magnetic resonance imaging (MRI) is still being explored as a diagnostic tool but its value remains to be determined.
At the time of EC’s diagnosis and treatment, the standard of care included an anthracycline-based neoadjuvant regimen, mastectomy, then adjuvant chemotherapy and radiotherapy. The neoadjuvant use of doxorubicin and cyclophosphamide followed by treatment with adjuvant docetaxel subscribes to the standard.
For nearly 2 years EC did well and returned to her active lifestyle. Her experience unearthed a desire to educate others about IBC. When a physician appointment to evaluate right quadrant abdominal pain suggested a possible ovarian cyst, she tried not to worry. Laparoscopic surgery revealed metastasis to the ovaries, so they were removed. Chemotherapy was used to control the disease, but over the course of the next year skeletal metastasis developed. Additional regimens of chemotherapy and radiotherapy were tried but failed to stop the metastatic IBC, which spread to the lung. As the disease continued to advance, EC decided against additional chemotherapy in an effort to conserve her energy to spend more time with her family. A few months later, EC died at 42 years of age.
Unfortunately, an aggressive disease course culminating in death is not uncommon in patients with IBC. Reports vary, but patients with IBC generally have a poor prognosis, with a 5-year survival ranging from 30% to 50%. Nevertheless, IBC can be as diverse as the people affected. In spite of increased awareness and research, IBC remains poorly understood.
Diagnosis is based on subjective criteria often mistaken for mastitis or cellulitis, delaying important treatment. Controversy exists regarding the actual incidence of the disease, with estimates ranging from 1% to 5% of cases,[3,4] and until recently IBC was considered a subset of locally advanced breast cancer and often confused with neglected breast cancer (ie, breast lesions eventually erupting through the skin in patients who delayed seeing a medical professional; while similar in appearance to IBC, these symptoms develop over a much longer period of time). IBC is more common in younger women and affects African-American woman disproportionately.
The National Comprehensive Cancer Network (NCCN) recently added a Practice Guideline specific to inflammatory breast cancer that advises oncologists on the management of patients with IBC and helps to define the disease as a distinct entity. Dr. Robert W. Carlson, Chair of the NCCN breast panel, is quoted in the group’s 2008 conference report as stating that, “Clinically, this [IBC] looks like cellulitis of the breast, and any cellulitis of the breast that occurs in a nongravid, nonlactating woman should be assumed to be inflammatory breast cancer until proved otherwise.” These are important words to the medical community, who often dismiss the symptoms as hormone-related, contact dermatitis, or even simply a result of stress.
With the recognition of IBC as a distinct entity, perhaps research into IBC will become more attractive to those developing new therapeutic agents. Research seeking drugable targets has zeroed in on NF-kappa B, EGFR 2, and p53, for example, in an attempt to improve overall survival.[7,8] The heterogeneity of the disease complicates finding a “one size fits all” therapeutic regimen that will be effective in all IBC patients. Some research shows a higher incidence of estrogen negativity, ERBB2 positivity (2+ or 3+), and high E-cadherin in IBC, but not all cases bear this molecular signature. Fortunately, newer clinical trial reports note the number of IBC patients in the study. Having these disease-specific data will help to define evidence-based treatment protocols.
In 1999, the Inflammatory Breast Cancer Research Foundation (www.ibcresearch.org) was established with the two-fold mission to raise awareness and facilitate research into IBC. This internet-based nonprofit organization provides an extensive website, email discussion lists, and printed literature, as well a means of connecting those in the IBC community. Inflammatory Breast Cancer Research Foundation volunteers are available to communicate with newly diagnosed individuals or answer questions by internet or telephone.
In 2005, the organization launched the Inflammatory Breast Cancer Research Foundation BioBank and Clinical Data Base in an effort to make available de-identified biospecimens and their associated data to the research community. This project is owned and operated by the advocacy organization under the guidance of a Medical Advisory Board. Through a variety of collaborative efforts, the Inflammatory Breast Cancer Research Foundation is helping to move research from bench to bedside and will remain an active partner in the breast cancer research community.
Several specialty clinics have opened that focus on the management and study of IBC. In 2004, Odette Cancer Centre, in Toronto, opened a clinic devoted to locally advanced and inflammatory breast cancer. This was followed by the Morgan Welch Inflammatory Breast Cancer Clinic at The University of Texas, M. D. Anderson Cancer Center in the fall of 2006.
A year later, in 2007, the University of Michigan, Ann Arbor, established an IBC clinic.
In addition to these clinics, there are numerous physicians in the U.S. with expertise in the diagnosis and treatment of IBC, many located in larger cancer centers throughout the nation. Patients should explore options and seek out a health care professional with experience when dealing with this atypical form of breast cancer.
Breast cancer research has made amazing strides with the advent of taxanes and targeted therapies, but unfortunately IBC patients have not received the same benefit from these advances. A 30-year study, assessing 329 IBC patients in a single institution came to the following conclusion: “Our data show that there has not been an important change in the prognosis of patients with IBC ... in the last 30 years.” This study created an uproar in the patient community, but the data speak for themselves.
Since Sir Charles Bell first described this condition in 1814, and Lee and Tannebaum added to that description and provided the name “inflammatory breast cancer” in 1924, we still lack a 21st century, molecular definition of this aggressive disease. As long as IBC research remains fragmented, underfunded, and limited in scope, patients will continue to die in spite of our best efforts. The lay and medical communities need to know the symptoms of IBC and not ignore suspicious changes. Breast cancer education should stress awareness of visible changes to the breast in addition to the importance of checking for lumps and obtaining regular mammograms.
Financial Disclosure:The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.
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