- Email: [email protected]
Inflammatory Breast Cancer: Patient Advocate View
Inflammatory Breast Cancer: Patient Advocate View Ginny Mason and Owen Johnson Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer, often presenting with distant metastasis. While controversy exists regarding the actual incidence of the disease, there is agreement that IBC causes a disproportionate number of breast cancer deaths. Those with typical IBC symptoms face a healthcare system that is often dismissive of their concerns. This is especially true for pregnant, lactating, and younger women. IBC remains poorly understood and diagnosis is frequently delayed due to a lack of knowledge in both the lay and medical communities. The IBC Research Foundation is committed to facilitating research that will improve diagnosis and treatment of IBC, as well as working to raise awareness of the disease in the medical community and general population. Semin Oncol 35:87-91 © 2008 Elsevier Inc. All rights reserved.
T
hanks to courageous and outspoken women like Betty Ford and Happy Rockefeller,1 public discussion of breast cancer is no longer taboo.
Weeks after Betty Ford became First Lady, she underwent a mastectomy for breast cancer on September 28, 1974. Her openness about her illness raised the visibility of a disease that Americans had previously been reluctant to talk about. “When other women have this same operation, it doesn’t make any headlines,” she told Time magazine. “But the fact that I was the wife of the President put it in headlines and brought before the public this particular experience I was going through. It made a lot of women realize that it could happen to them. I’m sure I’ve saved at least one person—maybe more.” Further amplifying the public awareness of breast cancer were reports that several weeks after Betty Ford’s cancer surgery, Happy Rockefeller, the wife of vice president Nelson Rockefeller, also underwent a mastectomy.
Inflammatory Breast Cancer Research Foundation, Bainbridge Island, WA. Address correspondence to Ginny Mason, RN, BSN Inflammatory Breast Cancer Research Foundation, 321 High School Road NE, STE D3 #149, Bainbridge Island, WA 98110. E-mail: [email protected] 0270-9295/08/$ - see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1053/j.seminoncol.2007.11.011
Seminars in Oncology, Vol 35, No 1, February 2008, pp 87-91
Open any women’s magazine, especially in October, and you will be confronted with articles on early detection, breast cancer treatment and a variety of personal stories of breast cancer survival. Along with these articles will be numerous ‘pink marketing’ advertisements,2 as well as pink ribbons throughout, designed to grab attention and pluck our heartstrings. If breast cancer has “come out of the closet,” why is it that so few people know about inflammatory breast cancer (IBC)? Why, when the public is frequently reminded by the media to have regular mammograms and check for breast lumps, is the incidence of late-stage breast cancer not decreasing?3 And why, in this scientific age, is IBC still only a clinical diagnosis based on the subjective observations of a clinician, with no specific histology or identified molecular abnormalities?
IMPROVEMENTS: BUT NOT FOR ALL? Advances in the diagnosis and treatment of breast cancer have had a powerful impact in recent years. The advent of breast-conserving therapy, sentinel lymph node dissection, and improved imaging techniques has changed the prognosis and treatment of early-stage breast cancer to a potentially curable disease.4 The use of tamoxifen, to reduce recurrence in estrogen receptor–positive breast cancer, and trastuzamab, in the treatment of those with Her2/neu–positive disease, has ushered in a new era of effective targeted therapy. Unfortunately, these advances have had minimal benefit for the IBC patient community.5 A recent study by M.D. Anderson Cancer Center evaluated 398 IBC patients treated between 1974 and 2005.5 The following quote is from the article; “Despite 87
88
G. Mason and O. Johnson
the clear stepwise advances that are being made in the adjuvant treatment of breast cancer, a favorable effect of new therapies on the survival of patients with IBC has not been established.” After the data were mined and analyzed, it was concluded that “there has not been an important change in the prognosis of patients with IBC in the last 30 years.”6 The IBC patient and advocacy community was stunned by the M.D. Anderson study. We wanted to believe that recent advances had deemed the old statistics obsolete and skewed the prognosis statistics in favor of long-term survival. As this study was shared on the e-mail discussion list of the IBC Research Foundation, emotion-filled messages were plentiful, revealing fears and eroding hope. One participant wrote:
“I’m trying to respond intellectually rather than emotionally; I just have to express that I dread getting these links to articles that seem always to conclude that nothing is improving in IBC care, that survivorship is not improving, etc. etc. Is there no good news for those of us cursed with this disease?” Another shared these thoughts:
“I am told I will be doing Herceptin the rest of my life, but I’m still only 34 years old, so if I live long enough, I hope to see a cure before I get to the ‘rest of my life.’ This article certainly doesn’t give me much hope though.” IS IBC A DISTINCT DISEASE? Most current breast literature categorizes IBC as a form of locally advanced breast cancer (LABC). This classification would lead one to believe that IBC is just a neglected breast cancer gaining attention when the skin becomes involved and the patient experiences physical symptoms that encourage medical intervention. This theory is contradicted by those individuals participating in the IBC Research Foundation e-mail discussion list. Frequently, patients share that their symptoms appeared almost overnight and often just weeks or months after a negative mammogram. If indeed IBC is just a neglected breast cancer, the symptoms should have a slow, gradual onset. During the 2006 San Antonio Breast Cancer Symposium, Dr Massimo Cristofanilli stated that he believes IBC is a distinct entity, not a form of locally advanced breast cancer. This statement was made during response to questions following the presentation of data from the IBC specific clinical trials using the tyrosine kinase inhibitor, lapatinib. Dr Cris-
tofanilli also strongly stressed the need for more study and clinical trials focusing on IBC.7 In a 2003 Journal of Clinical Oncology article, Dr William F. Anderson and colleagues raised the controversial issue of IBC as a distinct clinicopathologic entity.8 Using Surveillance, Epidemiology, and EndResults (SEER) program data they compared tumor characteristics, prognosis, and age-specific incidence rate patterns to determine if IBC and LABC were different. They concluded that IBC and LABC seemed to be distinct biologic entities with different prognostic factor profiles and age-specific incidence rate patterns. Dr Sanford Barsky, chair of the department of pathology at Ohio State University, has been studying the unique characteristics of IBC for much of his career. Dr Barsky developed a mouse model of IBC, Mary-X. Through his work with Mary-X, Dr Barsky has written repeatedly about the florid lymphovascular invasion (LVI) or lymphovascular tumor emboli that occur very early in the development of IBC. Lymphovascular emboli are clumps of tumor cells within lymphovascular spaces.9 He has hypothesized that these tumor emboli escape the breast very early, forming distant metastasis. It is usually assumed that most cases of IBC involve the axillary lymph nodes. This presentation makes early detection extremely difficult using current imaging techniques, although breast imaging is usually a part of the diagnostic process. Typically IBC is not detected by mammogram or ultrasound, but there are exceptions. Mammographic patterns associated with IBC commonly show skin thickening and diffuse increased breast density. With IBC more common in younger women, dense breast tissue is expected, but such mammographic findings require further evaluation.10 The unique development, presentation, and metastatic spread of IBC, coupled with the observations of clinicians experienced in the treatment of IBC and the review of SEER data, all support the belief that IBC is a distinct disease entity and should be seen and treated as such.
CONCERNS OF THE ADVOCACY COMMUNITY Increased awareness of IBC is certainly important so that patients with worrisome symptoms will know to seek out medical intervention. Also, the medical community needs adequate education so typical symptoms will be recognized. Once suspected, a protocol should be available to guide evaluation. As important as awareness is, the prognosis for those diagnosed with IBC will not improve without dedicated, high-quality research. Facilitating such research is the primary goal of the IBC Research Foundation. Early IBC pioneers Lee and Tannenbaum wrote, “It (IBC) is often fulminating and may result fatally in a
Patient advocate view of IBC
short time in spite of the most intelligent therapeutic efforts to control it.”11 Unfortunately, little more has been learned about this deadly disease and the outcome often remains the same. Dr Barsky’s work with the Mary-X xenograft mouse, the use of limited cells lines, and, more recently, human tissue samples have yet to provide adequate data to change the course of diagnosis and treatment of IBC.
RESEARCH EMPHASIS The IBC Research Foundation uses the signature slogan, “committed to finding the cause.” Prevention is only a dream when the cause is unknown. Until the cause of IBC is identified the search continues. There is extensive literature examining various environmental, dietary, and other potential carcinogenic factors in our lives but little hard evidence that can show a direct, causal relationship to breast cancer. It has become clear that breast cancer in general is the result of multiple factors, not one simple thing. This is most likely the case with IBC as well, although even less is known about the etiology of IBC. The higher incidence of the disease in specific populations, such as African Americans12 and in countries of northern Africa (MAGHREB: Morocco, Algeria, Tunisia, and Egypt)9 could point to genetic or hereditary factors associated with IBC. Research planned for these geographic areas can compare the molecular signature of this disease with that of patients in the United States. Recently published reports of the higher incidence of triple-negative (estrogen- and progesterone-negative, Her2/neu-negative) aggressive breast cancer in young African American women raise new questions in relation to race, ethnicity, and IBC.13 The name inflammatory breast cancer or carcinoma comes from the early descriptions of the physical features of the disease. The swollen, red, tender, and painful breast resembles the breast infection mastitis. This appearance prompted the name inflammatory. With more recent attention to the potential role of chronic inflammation and the inflammatory response in the development of cancer, perhaps it is time to explore this hypothesis with IBC. SEER data indicate that the incidence of IBC has increased. “In the 3-year intervals between 1988 and 1990 and 1997 and 1999, the age-adjusted incidence rate of IBC rose by 25%.”10 The rather narrow definition of IBC used by SEER could skew the incidence data. A clearly defined IBC case definition is needed to provide an accurate estimate of IBC incidence rates and a less subjective form of diagnosis.
EARLY DETECTION? The most readily available forms of breast imaging have not been proven useful in the detection of IBC
89
without a solid mass. Dedicated breast magnetic resonance imaging (MRI) and ultrasound may prove useful in staging the disease, but the utility of these studies in diagnosis has not been robust. Contrast-enhanced dedicated breast MRI has shown utility in monitoring response to treatment and may provide useful information regarding tissue response.14 Current diagnosis relies on a skin punch, core needle, or surgical biopsy to validate the clinical diagnosis. The presence of dermal lymphatic invasion or lymphovascular invasion is a classic pathological hallmark of IBC. The absence of a palpable or mammographic mass often causes hesitation, on the part of the surgeon, to proceed with an invasive procedure like biopsy. Patients end up frustrated in their efforts to find a physician willing to do what is necessary to determine the cause of their symptoms. A non-invasive or minimally invasive diagnostic test, with high sensitivity and specificity, is essential if IBC is to be detected at the onset of symptoms.
IMPROVED TREATMENT MODALITIES The treatment of breast cancer in general, has followed a “one size fits all” model. Factors determining treatment include tumor size, lymph node involvement, estrogen and progesterone receptor activity, and more recently Her2/neu status of the tumor. Individual physicians may have a protocol of choice based on their specific training, but there continue to be basic chemotherapy protocols that are traditionally used. When treating IBC, this same principal has been applied. The heterogeneity of IBC complicates the design of a protocol that will work to control the disease in all patients. The gold standard has been an anthracycline (like doxorubicin), cyclophosphamide, and one of the taxane drugs. Prior to the advent of taxanes in the treatment of breast cancer, 5-fluorouracil was the standard third component of the triple cocktail. This combination is effective in some but certainly not all patients. The use of neoadjuvant chemotherapy allows the clinician to observe visible changes in the affected breast. Unfortunately, it often takes several sessions of chemotherapy to determine if the standard regimen is effective, losing precious time when dealing with primary IBC. The identification of specific biological markers that could be exploited in the treatment of IBC would have a significant impact on overall survival. In the absence of those specific IBC biomarkers for treatment choice, patients often turn to various available tests that claim the ability to predict which chemotherapy agents will be best suited to treat their particular tumor tissue. These in vitro tests are well marketed and patients desperately want to believe that the tests will give “the answer” that will produce survival. In another potential treatment approach, Dr Barsky suggests focusing on the lymphovascular emboli and
90
finding ways to disadhere cells from the tumor emboli to destroy tumor cells.9 A study at the City of Hope Comprehensive Cancer Center in California reported that stage IIIB IBC patients could benefit from single or tandem dose-intense chemotherapy.15 Still others are focusing on molecular profiling in an attempt to identify upregulated genes that could provide diagnostic or prognostic markers that might form the basis of novel therapeutics.16
WHAT CAN WE DO? As members of the IBC patient advocacy community we have a responsibility to raise awareness of IBC, encourage participation in clinical trials, and partner with the breast cancer research community to increase research of IBC. One way the IBC Research Foundation has found to facilitate research is through the development and implementation of the IBC Research Foundation BioBank and Clinical Data Base. In the years since the organization’s start, we have been told that it is difficult to find a geographic cohort to use in the study of IBC. Having an advocacy-owned and -operated IBC biorepository, complete with associated medical records, has the potential to move IBC research from bench to bedside in a more timely manner. This project also brings patients and researchers into a new collaborative model. The IBC Research Foundation BioBank and Clinical Data Base is a novel, patient-driven long-term research project that enables patients to partner in a wide variety of research projects even after their deaths. Under the guidance and direction of a highly qualified Medical Advisory Board and the organization’s Board of Directors, the BioBank has approved providing biospecimens for research purposes following a detailed Institutional Review Board–approved protocol. Through projects like the BioBank, the IBC Research Foundation is able to model moving patient advocacy in a new direction and realize our mission to facilitate meaningful research.
CONCLUSION Despite the great strides in the general field of breast cancer, IBC remains a disease in the shadows. Most people do not know about the disease until they or someone close to them is diagnosed. Sadly, many in the medical community are not familiar with IBC or believe it is so rare they will not encounter a case. Herculean efforts are needed to raise awareness and advocate for increased research if improvements in the diagnosis, treatment, and prognosis of IBC are to occur. The IBC community includes patients, family members, and other concerned people who are willing to work for these changes. It is our desire to
G. Mason and O. Johnson
be an equal partner as we work together to change the course of IBC.
Acknowledgment The authors gratefully acknowledge the efforts of the many clinicians and basic researchers who work tirelessly to further the knowledge of IBC. To the many volunteers who serve as patient advocates in the IBC community, we offer our thanks. Together, we will continue our work to end the pain and suffering of this deadly disease and seek improved diagnosis, treatment outcomes, and eventually prevention and cure.
REFERENCES 1. Breast cancer: fears and facts. Time. November 4, 1974. http://www.time.com/time/magazine/article/ 0,9171,945077,00.html. 2. Breast Cancer Action: http://www.thinkbeforeyoupink. org/Pages/AboutTheCampaign.html. 3. SEER. http://canques.seer.cancer.gov. 4. Guarneri V, Conte PF. The curability of breast cancer and the treatment of advanced disease. Eur J Nucl Med Mol Imaging. 2004;31 Suppl 1:S149-61. 5. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. Trastuzumab after adjuvant chemotherapy in Her 2-positive breast cancer. N Engl J Med. 2005;353: 59-72. 6. Gonzalez-Angulo AM, Hennessy BT, Broglio K, et al. Trends for inflammatory breast cancer: is survival improving? Oncologist. 2007;12:904-12. 7. Cristofanilli M, Boussen H, Baselga J, et al. A phase II combination study of lapatinib and pacletaxel as a neoadjuvant therapy in patients with newly diagnosed inflammatory breast cancer. (IBC) Presented at the San Antonio Breast Cancer Symposium; 2006 Dec 14; San Antonio, TX. 8. Anderson WF, Chu KC, Chang S. Inflammatory breast carcinoma and non-inflammatory locally advanced breast carcinoma: distinct clinicopathologic entities? J Clin Oncol. 2003;21:2254-9. 9. Barsky SH. Inflammatory breast cancer: few survivors, fewer baby boomer advocates. Oncologistics. Third Quarter: 26-33, 2006. 10. Hance KW, Anderson WF, Devesa SS, et al. Trends in inflammatory breast carcinoma incidence and survival: the Surveillance, Epidemiology, and End Results program at the National Cancer Institute. J Natl Cancer Inst. 2005;97:966-75. 11. Lee BJ, Tannenbaum NE. Inflammatory carcinoma of the breast: a report of twenty-eight cases from the Breast Clinic of the Memorial Hospital. Surg Gynecol Obstet. 1924;39:580-95. 12. Cristofanilli M, Buzdar AU, Hortobágyi GN, et al. Update on the management of inflammatory breast cancer. Oncologist. 2003;8:141-8. 13. Carey LA, Perou CM, Livasy CA, et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA. 2006;295:2492-502.
Patient advocate view of IBC
14. Thukral A, Thomasson DM, Chow CK, et al. Inflammatory breast cancer: dynamic contrast-enhanced MR in patients receiving bevacizumab—initial experience. Radiology. 2007;244:727-35. 15. Somlo G, Frankel P, Chow W, et al. Prognostic Indicators and survival in patients with stage IIIB inflammatory
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breast carcinoma after dose-intense chemotherapy. J Clin Oncol. 2004;22:1839-48. 16. Van Laere S, Van der Auwera I, Van den Eynden GG, et al: Distinct molecular signature of inflammatory breast cancer by cDNA microarray analysis. Breast Cancer Res Treat. 2005;93:237-46.
T
hanks to courageous and outspoken women like Betty Ford and Happy Rockefeller,1 public discussion of breast cancer is no longer taboo.
Weeks after Betty Ford became First Lady, she underwent a mastectomy for breast cancer on September 28, 1974. Her openness about her illness raised the visibility of a disease that Americans had previously been reluctant to talk about. “When other women have this same operation, it doesn’t make any headlines,” she told Time magazine. “But the fact that I was the wife of the President put it in headlines and brought before the public this particular experience I was going through. It made a lot of women realize that it could happen to them. I’m sure I’ve saved at least one person—maybe more.” Further amplifying the public awareness of breast cancer were reports that several weeks after Betty Ford’s cancer surgery, Happy Rockefeller, the wife of vice president Nelson Rockefeller, also underwent a mastectomy.
Inflammatory Breast Cancer Research Foundation, Bainbridge Island, WA. Address correspondence to Ginny Mason, RN, BSN Inflammatory Breast Cancer Research Foundation, 321 High School Road NE, STE D3 #149, Bainbridge Island, WA 98110. E-mail: [email protected] 0270-9295/08/$ - see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1053/j.seminoncol.2007.11.011
Seminars in Oncology, Vol 35, No 1, February 2008, pp 87-91
Open any women’s magazine, especially in October, and you will be confronted with articles on early detection, breast cancer treatment and a variety of personal stories of breast cancer survival. Along with these articles will be numerous ‘pink marketing’ advertisements,2 as well as pink ribbons throughout, designed to grab attention and pluck our heartstrings. If breast cancer has “come out of the closet,” why is it that so few people know about inflammatory breast cancer (IBC)? Why, when the public is frequently reminded by the media to have regular mammograms and check for breast lumps, is the incidence of late-stage breast cancer not decreasing?3 And why, in this scientific age, is IBC still only a clinical diagnosis based on the subjective observations of a clinician, with no specific histology or identified molecular abnormalities?
IMPROVEMENTS: BUT NOT FOR ALL? Advances in the diagnosis and treatment of breast cancer have had a powerful impact in recent years. The advent of breast-conserving therapy, sentinel lymph node dissection, and improved imaging techniques has changed the prognosis and treatment of early-stage breast cancer to a potentially curable disease.4 The use of tamoxifen, to reduce recurrence in estrogen receptor–positive breast cancer, and trastuzamab, in the treatment of those with Her2/neu–positive disease, has ushered in a new era of effective targeted therapy. Unfortunately, these advances have had minimal benefit for the IBC patient community.5 A recent study by M.D. Anderson Cancer Center evaluated 398 IBC patients treated between 1974 and 2005.5 The following quote is from the article; “Despite 87
88
G. Mason and O. Johnson
the clear stepwise advances that are being made in the adjuvant treatment of breast cancer, a favorable effect of new therapies on the survival of patients with IBC has not been established.” After the data were mined and analyzed, it was concluded that “there has not been an important change in the prognosis of patients with IBC in the last 30 years.”6 The IBC patient and advocacy community was stunned by the M.D. Anderson study. We wanted to believe that recent advances had deemed the old statistics obsolete and skewed the prognosis statistics in favor of long-term survival. As this study was shared on the e-mail discussion list of the IBC Research Foundation, emotion-filled messages were plentiful, revealing fears and eroding hope. One participant wrote:
“I’m trying to respond intellectually rather than emotionally; I just have to express that I dread getting these links to articles that seem always to conclude that nothing is improving in IBC care, that survivorship is not improving, etc. etc. Is there no good news for those of us cursed with this disease?” Another shared these thoughts:
“I am told I will be doing Herceptin the rest of my life, but I’m still only 34 years old, so if I live long enough, I hope to see a cure before I get to the ‘rest of my life.’ This article certainly doesn’t give me much hope though.” IS IBC A DISTINCT DISEASE? Most current breast literature categorizes IBC as a form of locally advanced breast cancer (LABC). This classification would lead one to believe that IBC is just a neglected breast cancer gaining attention when the skin becomes involved and the patient experiences physical symptoms that encourage medical intervention. This theory is contradicted by those individuals participating in the IBC Research Foundation e-mail discussion list. Frequently, patients share that their symptoms appeared almost overnight and often just weeks or months after a negative mammogram. If indeed IBC is just a neglected breast cancer, the symptoms should have a slow, gradual onset. During the 2006 San Antonio Breast Cancer Symposium, Dr Massimo Cristofanilli stated that he believes IBC is a distinct entity, not a form of locally advanced breast cancer. This statement was made during response to questions following the presentation of data from the IBC specific clinical trials using the tyrosine kinase inhibitor, lapatinib. Dr Cris-
tofanilli also strongly stressed the need for more study and clinical trials focusing on IBC.7 In a 2003 Journal of Clinical Oncology article, Dr William F. Anderson and colleagues raised the controversial issue of IBC as a distinct clinicopathologic entity.8 Using Surveillance, Epidemiology, and EndResults (SEER) program data they compared tumor characteristics, prognosis, and age-specific incidence rate patterns to determine if IBC and LABC were different. They concluded that IBC and LABC seemed to be distinct biologic entities with different prognostic factor profiles and age-specific incidence rate patterns. Dr Sanford Barsky, chair of the department of pathology at Ohio State University, has been studying the unique characteristics of IBC for much of his career. Dr Barsky developed a mouse model of IBC, Mary-X. Through his work with Mary-X, Dr Barsky has written repeatedly about the florid lymphovascular invasion (LVI) or lymphovascular tumor emboli that occur very early in the development of IBC. Lymphovascular emboli are clumps of tumor cells within lymphovascular spaces.9 He has hypothesized that these tumor emboli escape the breast very early, forming distant metastasis. It is usually assumed that most cases of IBC involve the axillary lymph nodes. This presentation makes early detection extremely difficult using current imaging techniques, although breast imaging is usually a part of the diagnostic process. Typically IBC is not detected by mammogram or ultrasound, but there are exceptions. Mammographic patterns associated with IBC commonly show skin thickening and diffuse increased breast density. With IBC more common in younger women, dense breast tissue is expected, but such mammographic findings require further evaluation.10 The unique development, presentation, and metastatic spread of IBC, coupled with the observations of clinicians experienced in the treatment of IBC and the review of SEER data, all support the belief that IBC is a distinct disease entity and should be seen and treated as such.
CONCERNS OF THE ADVOCACY COMMUNITY Increased awareness of IBC is certainly important so that patients with worrisome symptoms will know to seek out medical intervention. Also, the medical community needs adequate education so typical symptoms will be recognized. Once suspected, a protocol should be available to guide evaluation. As important as awareness is, the prognosis for those diagnosed with IBC will not improve without dedicated, high-quality research. Facilitating such research is the primary goal of the IBC Research Foundation. Early IBC pioneers Lee and Tannenbaum wrote, “It (IBC) is often fulminating and may result fatally in a
Patient advocate view of IBC
short time in spite of the most intelligent therapeutic efforts to control it.”11 Unfortunately, little more has been learned about this deadly disease and the outcome often remains the same. Dr Barsky’s work with the Mary-X xenograft mouse, the use of limited cells lines, and, more recently, human tissue samples have yet to provide adequate data to change the course of diagnosis and treatment of IBC.
RESEARCH EMPHASIS The IBC Research Foundation uses the signature slogan, “committed to finding the cause.” Prevention is only a dream when the cause is unknown. Until the cause of IBC is identified the search continues. There is extensive literature examining various environmental, dietary, and other potential carcinogenic factors in our lives but little hard evidence that can show a direct, causal relationship to breast cancer. It has become clear that breast cancer in general is the result of multiple factors, not one simple thing. This is most likely the case with IBC as well, although even less is known about the etiology of IBC. The higher incidence of the disease in specific populations, such as African Americans12 and in countries of northern Africa (MAGHREB: Morocco, Algeria, Tunisia, and Egypt)9 could point to genetic or hereditary factors associated with IBC. Research planned for these geographic areas can compare the molecular signature of this disease with that of patients in the United States. Recently published reports of the higher incidence of triple-negative (estrogen- and progesterone-negative, Her2/neu-negative) aggressive breast cancer in young African American women raise new questions in relation to race, ethnicity, and IBC.13 The name inflammatory breast cancer or carcinoma comes from the early descriptions of the physical features of the disease. The swollen, red, tender, and painful breast resembles the breast infection mastitis. This appearance prompted the name inflammatory. With more recent attention to the potential role of chronic inflammation and the inflammatory response in the development of cancer, perhaps it is time to explore this hypothesis with IBC. SEER data indicate that the incidence of IBC has increased. “In the 3-year intervals between 1988 and 1990 and 1997 and 1999, the age-adjusted incidence rate of IBC rose by 25%.”10 The rather narrow definition of IBC used by SEER could skew the incidence data. A clearly defined IBC case definition is needed to provide an accurate estimate of IBC incidence rates and a less subjective form of diagnosis.
EARLY DETECTION? The most readily available forms of breast imaging have not been proven useful in the detection of IBC
89
without a solid mass. Dedicated breast magnetic resonance imaging (MRI) and ultrasound may prove useful in staging the disease, but the utility of these studies in diagnosis has not been robust. Contrast-enhanced dedicated breast MRI has shown utility in monitoring response to treatment and may provide useful information regarding tissue response.14 Current diagnosis relies on a skin punch, core needle, or surgical biopsy to validate the clinical diagnosis. The presence of dermal lymphatic invasion or lymphovascular invasion is a classic pathological hallmark of IBC. The absence of a palpable or mammographic mass often causes hesitation, on the part of the surgeon, to proceed with an invasive procedure like biopsy. Patients end up frustrated in their efforts to find a physician willing to do what is necessary to determine the cause of their symptoms. A non-invasive or minimally invasive diagnostic test, with high sensitivity and specificity, is essential if IBC is to be detected at the onset of symptoms.
IMPROVED TREATMENT MODALITIES The treatment of breast cancer in general, has followed a “one size fits all” model. Factors determining treatment include tumor size, lymph node involvement, estrogen and progesterone receptor activity, and more recently Her2/neu status of the tumor. Individual physicians may have a protocol of choice based on their specific training, but there continue to be basic chemotherapy protocols that are traditionally used. When treating IBC, this same principal has been applied. The heterogeneity of IBC complicates the design of a protocol that will work to control the disease in all patients. The gold standard has been an anthracycline (like doxorubicin), cyclophosphamide, and one of the taxane drugs. Prior to the advent of taxanes in the treatment of breast cancer, 5-fluorouracil was the standard third component of the triple cocktail. This combination is effective in some but certainly not all patients. The use of neoadjuvant chemotherapy allows the clinician to observe visible changes in the affected breast. Unfortunately, it often takes several sessions of chemotherapy to determine if the standard regimen is effective, losing precious time when dealing with primary IBC. The identification of specific biological markers that could be exploited in the treatment of IBC would have a significant impact on overall survival. In the absence of those specific IBC biomarkers for treatment choice, patients often turn to various available tests that claim the ability to predict which chemotherapy agents will be best suited to treat their particular tumor tissue. These in vitro tests are well marketed and patients desperately want to believe that the tests will give “the answer” that will produce survival. In another potential treatment approach, Dr Barsky suggests focusing on the lymphovascular emboli and
90
finding ways to disadhere cells from the tumor emboli to destroy tumor cells.9 A study at the City of Hope Comprehensive Cancer Center in California reported that stage IIIB IBC patients could benefit from single or tandem dose-intense chemotherapy.15 Still others are focusing on molecular profiling in an attempt to identify upregulated genes that could provide diagnostic or prognostic markers that might form the basis of novel therapeutics.16
WHAT CAN WE DO? As members of the IBC patient advocacy community we have a responsibility to raise awareness of IBC, encourage participation in clinical trials, and partner with the breast cancer research community to increase research of IBC. One way the IBC Research Foundation has found to facilitate research is through the development and implementation of the IBC Research Foundation BioBank and Clinical Data Base. In the years since the organization’s start, we have been told that it is difficult to find a geographic cohort to use in the study of IBC. Having an advocacy-owned and -operated IBC biorepository, complete with associated medical records, has the potential to move IBC research from bench to bedside in a more timely manner. This project also brings patients and researchers into a new collaborative model. The IBC Research Foundation BioBank and Clinical Data Base is a novel, patient-driven long-term research project that enables patients to partner in a wide variety of research projects even after their deaths. Under the guidance and direction of a highly qualified Medical Advisory Board and the organization’s Board of Directors, the BioBank has approved providing biospecimens for research purposes following a detailed Institutional Review Board–approved protocol. Through projects like the BioBank, the IBC Research Foundation is able to model moving patient advocacy in a new direction and realize our mission to facilitate meaningful research.
CONCLUSION Despite the great strides in the general field of breast cancer, IBC remains a disease in the shadows. Most people do not know about the disease until they or someone close to them is diagnosed. Sadly, many in the medical community are not familiar with IBC or believe it is so rare they will not encounter a case. Herculean efforts are needed to raise awareness and advocate for increased research if improvements in the diagnosis, treatment, and prognosis of IBC are to occur. The IBC community includes patients, family members, and other concerned people who are willing to work for these changes. It is our desire to
G. Mason and O. Johnson
be an equal partner as we work together to change the course of IBC.
Acknowledgment The authors gratefully acknowledge the efforts of the many clinicians and basic researchers who work tirelessly to further the knowledge of IBC. To the many volunteers who serve as patient advocates in the IBC community, we offer our thanks. Together, we will continue our work to end the pain and suffering of this deadly disease and seek improved diagnosis, treatment outcomes, and eventually prevention and cure.
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Patient advocate view of IBC
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