ABSTRACT
Background: Although recognized as the most lethal breast cancer, inflammatory breast cancer (IBC), a NCI designated rare cancer and a cancer health disparity, is severely understudied. Given the unique presentation of diffuse tumor spread without a solid mass, not easily detected by selfbreast exams or mammograms, IBC patients often face delays in diagnosis and treatment leading to poor outcomes. Moreover, reproductive risk factors in IBC and high incidence in younger women, minoritized and marginalized populations highlight the significance of primary care providers (PCP) who are often the first point of contact when patients begin to notice symptoms. Method(s): In this study, we evaluated the knowledge gaps and barriers amongst PCP (physicians, physician assistants, nurse practitioners) in their ability to recognize the signs and coordinate care effectively for IBC. To assess PCP experiences with IBC in their practices and overall breast cancer care during COVID, we first conducted semi-structured interviews (n=11) with providers selected from a convenience sample at Duke University and in the local clinics. Based on data from these interviews and additional cognitive interviews, we developed and disseminated a comprehensive online survey (n=78). Result(s): In this study, access to care was identified as the single most important barrier to treating rare cancers. Furthermore, majority of the PCPs in this cohort identified only a moderate ability to recognize IBC in patients (mean = 3.3, range 1-7), thereby limiting early diagnosis. From the semi-structured interviews, PCPs recognized that IBC is not likely to be part of typical differential diagnosis when patients present with mastitis or breast changes, and most had not seen IBC in their practice. Only 31% (n=78) reported ever suspecting IBC in a patient. Delays in referrals to specialized large clinical centers were also reported as a major barrier. In particular, 62.8% (n=49) reported some delay in referrals for diagnostic imaging. In addition, since the COVID-19 pandemic started, 33% reported diagnosing less breast cancer cases and 63% reported that they experienced breast cancer referral delays. When asked what methods providers would find most helpful to learn more about diagnosing and caring for patients with IBC, the top three modes of preferred education were online CME options (53%);lunchtime, or other in-service training (33%);and website for patients and providers (32%). Conclusion(s): We succeeded in developing a survey instrument and to our knowledge first mixed methods study to assess PCP knowledge gaps and barriers to timely diagnosis and care of IBC patients. Results underscore need to develop PCP training modules and care coordination tools to improve guideline-concordant care. This survey instrument also has the potential to serve as a blueprint to design, implement, and evaluate interventions for other rare cancers.
ABSTRACT
Background. Lymphovascular invasion (LVI) and breast tumor emboli within dermal and breast lymphatic vessels are prognostic for metastatic spread and poor outcomes, and are abundant in Inflammatory breast cancer (IBC). IBC is an aggressive breast cancer that presents suddenly with breast swelling and redness due to tumor emboli in lymphatics. Lack of breast-feeding and obesity are IBC risk factors. We sought to demonstrate the combinatorial effects of a high-fat diet and nursing on lymphatic function and compare these to IBC tumor induced changes in lymphatic function. We hypothesize that risk factors for aggressive breast cancer may alter lymphatic function in the normal gland prior to tumor initiation. Methods. Following two rounds of pregnancy in 20 multiparous SCID Beige immunocompromised mice, half of the mice were force weaned while half nursed pups. Prior to forced weaning, half of each of these groups were fed a high fat diet (HFD: 60 Kcal %, N = 10) while the other half received a low-fat diet (LFD: 10 Kcal %, N = 10). Consecutive dynamic near-infrared fluorescence (NIRF) lymphatic imaging was performed at 6-7 months (covid interruption) and 14 months after initiating the diet by injecting a near-IR fluorophore into the mammary fatpad and recording lymphatic pulsing over 8 minutes using V++. Matlab and ImageJ were used to quantify pulsing rates on the ventral lymphatics in each animal. Fatpads were Ssubsequently inoculated with SUM149 IBC cells and imaging was repeated 16 months post diet initiation. Lymphatic imaging over time by HFD vs LFD was further studied in nulliparous animals. Tissues were collected for further analyses. ResultsData analysis prior to tumor injection, demonstrated lymphatic pulsing (pulses/4 minutes) increased over time in HFD force weaned (HFFW) and HFD nursing (HFN) animals only (65.5 vs 72.6, P=0.059;60.1 vs 76.6, P=0.0099, respectively). Comparing HFFW and HFN to matched LFD groups (LFFW and LFN), at 14 weeks HFD was associated with increased pumping after forced weaning (62.3 vs. 72.6, P=0.074), and nursing (62.5 vs 76.6, P=0.0023). There was an increase in pulsing after tumor initiation (16 months after initiation of diet) in all groups (80.1, 84.1, 83.2, 82.4, P > 0.05 all comparisons to initial timepoint). In a separate experiment examining HFD (N=5) vs LFD (N=5) in nulliparous mice, lymphatic contractile activity increased in all animals over. time, average ventral lymphatic contractile frequency for LFD and HFD at week 8, 11 and 14 weeks after diet initiation were 5, 8.64, 15.9 pumps/4 mins vs 11.8, 18.5, 28.2 pumps/4 mins, (P = 0.01, 0.05, and 0.0005 respectively). ConclusionsHFD increased lymphatic pulsing rate over time to a significantly greater extent than LFD continuing over 14 months independent of reproductive and nursing status. Tumor initiation prompted further increased pulsing rates beyond that observed after HFD across all groups. The magnitude of the effect of HFD on lymphatic pulsing approached the rate after tumor initiation, while reproductive variables did not impact lymphatic pulsing. Further studies are warranted to demonstrate the relationship if any between lymphatic pumping pre-initiation and LVI after tumor initiation and examine the role of intervention on reducing LVI.
ABSTRACT
INTRODUCTION AND IMPORTANCE: The initial misdiagnosis and delayed treatment for inflammatory breast cancer in men is brought about by its rarity and lack of readily available guidelines on pathways. CASE PRESENTATION: A 78-year-old male presented to the breast clinic with an abscess and was later diagnosed with inflammatory breast cancer. He presented with an abscess and was initially treated with antibiotics. Imaging showed a large left breast mass consistent with inflammatory carcinoma with axillary lymph node involvement. Patient was started on Tamoxifen as a bridge for surgery with no response. He eventually had a mastectomy and axillary clearance with the histology confirming the diagnosis and tumour emboli in the lymphatic vessels. Chemotherapy, radiation and dual hormone therapy were included in the adjuvant treatment plan. Two episodes of neutropenic sepsis led to completing only five out of six planned chemotherapy cycles. CLINICAL DISCUSSION: A review of literature and the reported cases was done by the team to contribute to the little information published about the disease and its management. The presented to the breast clinic during the height of the SARS- CoV-2 pandemic. The global impact of SARS-CoV-19 made surgical teams find ways to lessen elective lists to give way for patients affected during the pandemic. CONCLUSION: Very few cases of inflammatory breast cancer have been reported in men. The diagnosis can be missed leading to delay in management. Management can be challenging and complex.