Inflammatory Breast Cancer: Patterns of Failure and the Case for Aggressive Locoregional Management

Warren, Laura; Guo, Hao; Regan, Meredith M.; Nakhlis, Faina; Yeh, Edmund; Jacene, Heather A.; Hirshfield-Bartek, J; Overmoyer, Beth; Bellon, Jennifer R.

doi:10.1245/s10434-015-4469-4

Cited by 26 publications

(14 citation statements)

References 34 publications

(55 reference statements)

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“…Although a local failure in the setting of a DR has no impact on prognosis, LRR can negatively impact quality of life, particularly when associated with ulceration or bleeding. 14 The high rate of local failure among IFLBC patients seen in our study is comparable to that of prior reports, 15,16,17 despite maximal therapy, and supports the consensus statement by the International Expert Panel on Inflammatory Breast Cancer that following NAC, aggressive local therapy, including MRM and PMRT, remain the standard of care for IFLBC patients. 1 In contrast, the low rate of local failure observed among non-IFLBC T4 patients is similar to that seen in early-stage breast cancer patients treated with mastectomy 18 and supports trials examining surgical de-escalation or decreased use of radiotherapy in carefully selected patients with localized disease and an excellent response to NAC.…”

Section: Discussionsupporting

confidence: 89%

Does nonmetastatic inflammatory breast cancer have a worse prognosis than other nonmetastatic T4 cancers?

Romanoff

Zabor

Petruolo

et al. 2018

Cancer

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BACKGROUND: Both inflammatory (IFLBC) and non-inflammatory T4 (non-IFLBC) breast cancers have a heavy disease burden in the breast; whether IFLBC’s unique biology conveys a higher locoregional recurrence (LRR) risk and worse outcome versus other T4 lesions is uncertain. Here we compare outcomes in IFLBC and non-IFLBC patients treated with modern multimodality therapy. METHODS: Patients with non-metastatic T4 breast cancer treated with neoadjuvant chemotherapy, mastectomy, and radiation therapy between 2006–2016 were identified. Recurrences and survival were compared between IFLBC and non-IFLBC patients overall, and stratified by receptor subtype. RESULTS: Of 199 T4 patients, median age was 52yrs and median clinical tumor size was 7cm. 117 (59%) had IFLBC. At 41mos median follow-up, 4 patients had an isolated LRR, all occurring in IFLBC patients. 5-year isolated LRR in IFLBC patients was 4.8%. Overall, 14 patients had both LRR and distant recurrence (DR); 47 had DR only. 5-year distant recurrence-free survival (DRFS) was similar between IFLBC/non-IFLBC patients (63% vs 71%, log-rank p=0.14). 5-year DRFS was lowest (43%) among triple negative (TN) patients, and was significantly lower for TN IFLBC than non-IFLBC patients (28% vs 62%, log-rank p=0.02). 5-year overall survival (71% vs 74%, log-rank p=0.4) and cancer-specific survival (74% vs 79%, log-rank p=0.23) did not differ between IFLBC/non-IFLBC. CONCLUSIONS: Although IFLBC is often considered a unique biologic subtype, IFLBC and non-IFLBC patients had similar outcomes with modern multimodality therapy; isolated LRR was uncommon. TN subtype in IFLBC patients is associated with poor outcome, indicating the need for new treatment approaches in this group.

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Section: Discussionsupporting

confidence: 89%

Does nonmetastatic inflammatory breast cancer have a worse prognosis than other nonmetastatic T4 cancers?

Romanoff

Zabor

Petruolo

et al. 2018

Cancer

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“…A definitive diagnosis of IBC is made in a patient with these clinical symptoms and short timeline coupled with pathologic confirmation of invasive carcinoma3. Although IBC has a low incidence (about 2% in the United States124), it is the most lethal form of breast cancer with a median survival of approximately 4 years compared to >10 years for other non-inflammatory breast cancers (nIBC)456. A key characteristic of IBC distinguishing it from nIBC is IBC’s propensity for metastasis.…”

mentioning

confidence: 99%

“…A key characteristic of IBC distinguishing it from nIBC is IBC’s propensity for metastasis. Essentially all IBC patients present with lymph node involvement and one-third of patients already have distant metastasis at initial diagnosis1256. The survival curves for metastatic nIBC and non-metastatic IBC are nearly identical the first five years post diagnosis, further highlighting IBC’s characteristic lethality and rapid metastasis7.…”

mentioning

confidence: 99%

“…However, the overarching conclusion of these studies is that no molecular signature can be considered conclusive to adequately distinguish IBC from nIBC28. The 5 general molecular subtypes of nIBC (luminal A, luminal B, basal-like, HER2-enriched, and normal-like) are also represented in IBC, and IBC patients have a poorer prognosis regardless of the subtype56101314. A recent study determined that initial findings in differential gene expression between IBC and nIBC were in fact due to a difference in proportion of the 5 subtypes (IBC has fewer Luminal A and greater HER2-enriched cancers); when subtypes were directly compared, all IBC vs. nIBC expression differences disappeared10.…”

mentioning

confidence: 99%

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Macrophages Enhance Migration in Inflammatory Breast Cancer Cells via RhoC GTPase Signaling

Allen

Chen

Madden

et al. 2016

Sci Rep

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Inflammatory breast cancer (IBC) is the most lethal form of breast cancer. All IBC patients have lymph node involvement and one-third of patients already have distant metastasis at diagnosis. This propensity for metastasis is a hallmark of IBC distinguishing it from less lethal non-inflammatory breast cancers (nIBC). Genetic profiling studies have been conducted to differentiate IBC from nIBC, but no IBC cancer-cell-specific gene signature has been identified. We hypothesized that a tumor-extrinsic factor, notably tumor-associated macrophages, promotes and contributes to IBC’s extreme metastatic phenotype. To this end, we studied the effect of macrophage-conditioned media (MCM) on IBC. We show that two IBC cell lines are hyper-responsive to MCM as compared to normal-like breast and aggressive nIBC cell lines. We further interrogated IBC’s hyper-responsiveness to MCM using a microfluidic migration device, which permits individual cell migration path tracing. We found the MCM “primes” the IBC cells’ cellular machinery to become extremely migratory in response to a chemoattractant. We determined that interleukins −6, −8, and −10 within the MCM are sufficient to stimulate this enhanced IBC migration effect, and that the known metastatic oncogene, RhoC GTPase, is necessary for the enhanced migration response.

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“…IBC is known to be highly vascular that express a number of angiogenic factors such as vascular endothelial growth factor (VEGF). This encouraged a number of studies looking at the role of anti-VEGF agents (e.g., bevacizumab) combined with chemotherapy in the treatment of IBC, with hopeful results [5,6].…”

Section: Editorialmentioning

confidence: 99%

Management of Inflammatory breast cancer: current concepts

Alawad¹

2015

IJCRI

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International Journal of Case Reports and Images (IJCRI) is an international, peer reviewed, monthly, open access, online journal, publishing high-quality, articles in all areas of basic medical sciences and clinical specialties.Aim of IJCRI is to encourage the publication of new information by providing a platform for reporting of unique, unusual and rare cases which enhance understanding of disease process, its diagnosis, management and clinico-pathologic correlations.

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Inflammatory Breast Cancer: Patterns of Failure and the Case for Aggressive Locoregional Management

Cited by 26 publications

References 34 publications

Does nonmetastatic inflammatory breast cancer have a worse prognosis than other nonmetastatic T4 cancers?

Does nonmetastatic inflammatory breast cancer have a worse prognosis than other nonmetastatic T4 cancers?

Macrophages Enhance Migration in Inflammatory Breast Cancer Cells via RhoC GTPase Signaling

Management of Inflammatory breast cancer: current concepts

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