Posted on January 11, 2024

By Zoë Christopher, MA, BCAction Program Officer

Inflammatory Breast Cancer: Clinical Challenges, Evolving Concepts, and Novel Treatments

This year was the first year that inflammatory breast cancer (IBC) received attention on the main stage at SABCS. IBC is aggressive and rare (only 2–4% of breast cancer diagnoses are IBC), but it’s responsible for up to 10% of breast cancer-related deaths. It develops quickly and occurs when cancer cells block the lymphatic vessels in the skin covering the breast, creating a red, swollen, and inflamed appearance. 

IBC doesn’t often show up on a screening mammogram, and it’s not usually palpable as a lump in the breast. For these reasons, along with the inflamed appearance, doctors often misdiagnose and prescribe antibiotics. And due to the rapid development of IBC, by the time it’s accurately diagnosed, it’s usually stage III or IV. (According to the American Cancer Society, all IBC starts as stage III because it involves the skin, and becomes stage IV when it spreads outside the breast to other parts of the body.) Risk of developing IBC involves the same factors as non-IBC: age, family history, early menstruation, no childbirth, and previous breast cancer diagnoses. Risk also includes previous radiation therapy, obesity, and dense breast tissue. Currently there are no gene mutations associated specifically with IBC. 

Speaking to the challenges of accurately diagnosing IBC, Filipa Lynce, MD, assistant professor of medicine at Harvard Medical School and Director of the Dana-Farber Inflammatory Breast Cancer Program, noted that so little is known about this type of breast cancer, in comparison to more common types, that an accurate diagnosis is overly dependent on the doctor’s experience. We do know that a high proportion of IBC cases are triple negative or HER2 positive. We know that Black women have a 50% higher incidence of IBC than white women, with cases occurring at an earlier age, and with a greater mortality rate. A body mass index of 25 or more is also associated with IBC. But, unlike breast cancer in general, and with 40% of patients with IBC receiving the wrong diagnosis, this is a case in which more awareness and education is needed for both patients and clinicians.

Frederick M. Howard, MD, an instructor at the Elwood V. Jensen Scholar Program at the University of Chicago presented the question, “Is inflammatory breast cancer a genomically different type of breast cancer?” He noted that IBC remains a clinical diagnosis without highly specific molecular markers, and the genomic drivers of the disease are incompletely characterized. The overrepresentation of HER2 amplification and triple-negative disease within IBC have blurred comparisons between IBC and non-IBC. Nonetheless, some consistent genomic observations have emerged that may begin to explain the characteristic behavior of IBC, supported by both comparative clinical studies and preclinical models. 

Dr. Howard compared eight studies looking for genomic differences that would distinguish IBC from non-IBC. He concluded that the genomic differences are driven by hormone receptor subtype, that no gene expression signature consistently identifies IBC cases, and that there is no specific medical therapy unique or clearly more effective for IBC. Though there’s no unique genomic pattern, some studies have shown more frequent mutations in NOTCH (which may drive cancer stem cell-like behavior), DNA repair, and RAS/RAF pathways controlling for subtype, and that IBC does present unique microenvironment interactions, with inflammatory pathways seen on gene expression signatures. 

The treatment for IBC is similar to that of other types of locally advanced breast cancer (LABC). It usually includes neoadjuvant chemotherapy, surgery, and radiation therapy. Anthony Lucci, MD, professor at MD Anderson Cancer Center (MDACC), addressed the issue of treatment de-escalation as it’s related to IBC, and the controversies surrounding it. He writes: 

In an era of treatment de-escalation, there remain questions regarding the optimal surgical management for patients with inflammatory breast cancer (IBC). For years, the standard surgical approach for patients with IBC has been modified radical mastectomy (MRM) (including complete axillary node dissection as a component of MRM) with delayed breast reconstruction. In the recent past, some authors have proposed the use of breast conserving surgery, sentinel lymph node mapping, skin-sparing mastectomy, and even immediate reconstruction as possibly appropriate procedures for the treatment of patients with IBC.

Dr. Lucci reviewed the available data related to de-escalation of treatment, including what surgical procedures appear to provide the best outcomes for patients.

With IBC being difficult for clinicians to diagnose, Komen has developed a scoring system. The Komen IBC Scoring System proposes a set of diagnostic criteria to identify IBC. Criteria includes timing of symptoms, skin changes, swelling and/or engorgement, skin discoloration, nipple abnormalities, the use of lymphatic emboli, and breast imaging. It assigns timeframes for prevalence of less than 3 months (a numerical value of 3), 3–6 months (a value of 2), and more than 6 months (a value of 1). A score of less than 14 indicates negative for IBC, and 42 or more indicates positive for IBC, with “strong possibility” and “weak possibility” falling in between. Research is ongoing toward increasing diagnostic accuracy, guiding treatment decisions and inclusion in clinical trials, and aiding in basic future research.

MDACC opened an IBC multidisciplinary clinic in 2006 where they serve 125+ IBC patients a year. Trimodal therapy has given them the best outcomes, and consists of neoadjuvant chemotherapy, modified radical mastectomy (in which most of the underarm lymph nodes are also removed), and post-mastectomy radiation therapy. In spite of these findings, Dr. Lucci noted a recent IBC-focused survey revealed that a large percentage of clinicians did not follow the MDACC protocols. He also noted that as many as 40% of patients annually do not receive trimodal care. Is this because MDACC hasn’t effectively distributed this information to doctors? Is it because clinicians have overlooked IBC or don’t know enough about it? He didn’t speculate. 

Dr. Lucci also looked at several studies involving breast conserving therapy (lumpectomy) for IBC patients that, at first, seemed to indicate that it resulted in overall survival equal to modified radical mastectomy. But after pointing out the flaws in the comparisons and the rates of local regional recurrence (LRR), and accompanied by photographs of the negative surgical outcomes, he hoped he settled the controversy surrounding de-escalation of treatment. At the MDACC clinic, of 115 non-metastatic IBC patients in 2008–2016 that completed trimodal treatment, 98% had clear margins and after four years, 95% experienced LRR-free-survival. He concluded that longer follow-up is needed, but contemporary trimodal therapy with removal of all cancer cells at the tissue edges (resection to negative margins) produced LRR rates comparable to non-IBC.

The sentinel nodes are the first lymph nodes to which cancer will migrate, so a sentinel lymph node biopsy (SLNB) is often used to determine whether breast cancer has spread. But Dr. Lucci cited three studies that had revealed 18–25% false negative results for SLNB in IBC patients. A prospective feasibility trial of SLNB was reported on in 2017 involving 100 IBC patients. It revealed low identification rates and 20% false negative results. Despite these findings, a survey of 1096 patients with non-metastatic IBC diagnosed between 2012 and 2018 found a statistically significant increase in the use of SLNB that is not evidence-based or supported by current treatment guidelines. Dr. Lucci concluded that there is no clear data to support the idea that it is safe or accurate to perform SLNB in IBC patients.

Moving on to the issue of immediate reconstruction (IR) done at the time of initial surgery in IBC patients, Dr. Lucci addressed LRR and post-surgical complications. Citing four studies, he concluded there is not clear data to support the safety of IR. BCAction would conclude that IBC deserves attention and more research if we’re to understand and effectively treat it. It may be a small subset of breast cancer, but it deserves the same attention that triple negative and metastatic breast cancer are finally receiving.

Six panelists closed out the presentations. They included three advocates representing the IBC Network Foundation, the Inflammatory Breast Cancer Research Foundation, and the Inflammatory Breast Cancer Network UK. The advocates pointed out the gaps in treatment that need to be closed and the unmet needs that must be addressed:

  • They agreed with Dr. Lucci that treatment should not be de-escalated for this population.
  • We need more research to develop national standards of care to guide clinicians.
  • We need better understanding of cell lines and biomarkers.
  • We need improved and expanded diagnostic coding systems.
  • We need access to clinical trials for IBC specifically.
  • We need to lobby the Department of Defense for funding and research.

In order for providers to do a better job, advocates suggested:

  • Clinicians need to learn how to empower their patients to advocate for themselves.
  • They must become better listeners.
  • Even though IBC is rare, doctors must become more knowledgeable about it. Because IBC doesn’t usually involve a lump or a mammogram, patients often go to their primary care physician, and if that physician isn’t up-to-date on IBC diagnostic procedures and treatment, the patient is too often (40% of the time) misdiagnosed, which is particularly frightening in light of the rapid progression of this type of breast cancer.

IBC is an aggressive disease, with a historically reported five-year survival rate around 40%. But according to MDACC, advances in care are helping more patients live longer. Recent studies have shown that with the right treatment, IBC’s five-year survival rate is closer to 70% for stage III patients, and up to 50% for newly diagnosed stage IV patients. By the end of a data-filled afternoon at SABCS, I was reminded: in my problem-solving perfect world, we’d also study the successes. One of the advocates that participated in the panel discussion was diagnosed with IBC and given a 3% chance of survival—back in 1994! Why and how did that happen?