Targeting Inflammatory Breast Cancer: current and new treatments
Research Paper
Fatoumata Diallo
ENG 21003: Writing for the sciences
Professor Brittany Zayas
May 5, 2025
Introduction
Breast cancer is a form of cancer that occurs in women and can very rarely occur in men It is seen when either tumor suppressor or oncogenes mutate. Inflammatory Breast Cancer is a rare and extremely aggressive form of breast cancer. It only accounts for 1% to 6% (Chippa & Barazi, 2023) of all Breast Cancer. It is called “inflammatory” because some of the symptoms cause the breast to look inflamed due to cancer cells blocking lymph vessels in the skin. IBC typically does not have the same symptoms as other forms of breast cancer and does not always show up on mammograms making it harder to diagnose. There are many forms of Inflammatory breast cancer treatments, however, the most effective treatments are the Tri modality treatment; neoadjuvant chemotherapy, modified radical mastectomy, and Intensity-modulated proton therapy, as well as specific targeted therapies like trastuzumab and Pratuzumab.
Description
Inflammatory Breast Cancer is an aggressive and rapidly spreading form of breast cancer; it accounts for 2-4% of all breast cancers and is responsible for 7% of all breast cancer-related deaths (Chippa, Barazi, 2023). There are two subcategories of Inflammatory breast cancer: Primary IBC and Secondary IBC. In Primary IBC cancer develops in a healthy breast while in secondary the cancer recurs or shows up where a previous breast cancer occurred (Robertson et al., 2010). Most IBCs are hormone receptor-negative meaning they have shorter disease-free survival; IBC also has excessive amounts of HER2 proteins which lead to rapid growth of the tumor. The p53 tumor suppressor gene (TSG) plays a huge role in IBC, Mutation, or the increase of the p53 TSG happens in “20-50%” of all breast cancers including IBC. It is often associated with larger tumors and a higher chance of death, this becomes worse when the p53 tag is combined with negative estrogen receptors which only increases the risk of death (Chippa & Barazi, 2023 ) There was also an overexpression of the RhoC GTPase oncogene. The RhoC GTPase oncogene contributes to the aggression of IBC, it regulates mitosis but leads to rapid proliferation in cancer.
Symptoms of IBC include edema(swelling), erythema(redness), and orange peel appearance (Robertson et al., 2010). IBC spreads fast so often redness can cover 1/3 of the breast, also within a few days the skin can change from pink to dark red/purple (Fattahi et al., 2022). Doctors diagnose IBC in 2 ways; clinically and pathologically. Doctors use a core needle to confirm invasive cancer, and a skin biopsy shows a dermal lymphatic invasion (Chippa & Barazi, 2023). IBC can often be misdiagnosed with other conditions such as melanoma and other metastatic cancers. IBC is a rare and aggressive form of BC that is responsible for “8-10%” of all BC deaths (Chainitikun et al., 2021). There are many risk factors of IBC such as race, Obesity, and age. Black women and younger women have 50% higher IBC rates and worse survival rates compared to white women (Robertson et al., 2010). Obesity is a huge factor for IBC especially for women who go through menopause (Robertson et al., 2010). IBC has similar risk factors as other breast cancers such as if a woman has had previous radiotherapy or if they have a history including breast cancer.
Typical Treatment for IBC consists of a combination of chemotherapy, surgery, and radiation. Chemotherapy is an important type of systemic treatment because it shrinks the tumor before surgery. Studies have shown that Neoadjuvant chemotherapy has resulted in higher PCR
(pathologic complete response) rates in er negative IBC (Chainitikun et al., 2021). Higher PCR
rates can mean an increase in survival. Targeted therapies are another form of IBC treatment but
This limited information on them. If the cancer is HER-2 positive, targeted therapy
trastuzumab is given along with the chemo, sometimes along with another targeted drug,
Pertuzumab.
Tri modality Treatment
Tri modality treatment is the common treatment of IBC, it is a combination of systematic agents like surgery chemotherapy, and radiation. Clinical studies have proven that this type of treatment is highly effective. Neoadjuvant chemotherapy is administered first to shrink the tumor, then a mastectomy is performed, and lastly, radiation therapy is given to drain the lymphatics (Rueth et al., 2014). In a study where they tested the effects of the IBC treatment “66.8%” of the patients received more the trimodally treatment, it revealed that patients who underwent the Tri modality had the highest 5-year survival rates of “55.4%” compared to other patients who only received one or two systematic treatment (Rueth et al., 2014). Another study tested anthracycline-based chemotherapy and radiation, it resulted in a “74%” objective response rate (ORR) (Chainitikun et al., 2021).
Chemotherapy is an important systemic treatment because it shrinks the tumor before surgery. Neoadjuvant Chemotherapy can lead to PCR (pathological complete response) which in return increases survival rates. Anthracycline- and taxane-based chemotherapy is the standard treatment for IBC. Adding paclitaxel to the chemotherapy benefits the PCR and ER-negative patients. In addition, Mixing HDCT (high-dose chemotherapy) with AHSCT (Autologous Hematopoietic Stem Cell Transplantation) has been a failure due to toxicity and lack of survival.
Two types of surgeries can be used as a treatment for IBC; Modified radical mastectomy and Breast Conserving Surgery (BCS). A mastectomy is typically used but a study has shown the possibility for Breast Conserving Surgery. The study showed overall survival for Breast-Conserving Surgery was 70.3% (Adesoye et al., 2021), however, there is limited data, and the case was unlike regular Inflammatory Breast Cancer patients. There was another study based on Contralateral prophylactic mastectomy, which is surgically removing the unaffected breast when there is a high risk, but it showed a high mortality rate (Adesoye et al., 2021).
Radiation is a common treatment for IBC; it typically happens after chemotherapy and surgery. Radiation is very harsh and often extremely aggressive due to high dosages and is usually very toxic for IBC patients. A study was conducted to Test Intensity-modulated proton therapy (IMPT), a form of radiotherapy meant to target and shrink the tumor while minimizing exposure to other organs. IMPT reduces the toxicity of the radiation due to accurate rapid dose fall-off (Fattahi et al., 2022). In the study conducted in 2016-2020, they treated 19 IBC patients with adjuvant IMPT, which resulted in an overall survival rate of “89%” (Fattahi et al., 2022).
Targeted therapies
Targeted therapies are a form of Inflammatory breast cancer treatment they have taken with chemotherapy. However, there has been limited data on targeted therapy for IBC. There are many types of targeted therapies, and they are administered by the type of Inflammatory breast cancer. Trastuzumab, a standard anti-her2+ therapy is a key treatment because of HER2 overexpression, they are Higher levels of HER2 in IBC than other breast cancers. Trastuzumab plus chemotherapy has increased the overall survival rate in 5 years. Pertuzumab works as a HER2 and HER3 dimerization blocker, thus enhancing trastuzumab (Chainitikun et al., 2021). The Neo Sphere clinical trial tested THP (trastuzumab, pertuzumab, and chemotherapy) and showed that THP had the best PCR results. The Tryphena clinical trial tested the safety of dual anti-HER2 therapy, and the results were 50% PCR and low cardiac toxicity (Chainitikun et al., 2021). The Overmeyer study concentrated on neoadjuvant weekly paclitaxel + pertuzumab + trastuzumab, it revealed that 56% PCR and had low levels of toxicity (Chainitikun et al., 2021). Lapatinib blocks Her2 and EGFR (epidermal growth factor receptor regulates growth). The main clinical trials of lapatinib are GeparQuinto and NeoALTTO, but studies have shown that lapatinib has harsh side effects and is recommended against the use of it.
Conclusion
Overall, Inflammatory Breast Cancer is a rare and rapidly spreading form of breast cancer. IBC affects mostly black, younger, and obese women. IBC is seen when either tumor suppressor or oncogenes mutate, because of its aggressive nature IBC is harder to diagnose and treat. Typically, IBC is treated with surgery, chemotherapy, and radiation, but new treatments are being researched such as targeted therapies and other forms of radiation.
References
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Rueth, N. M., Lin, H. Y., Bedrosian, I., Shaitelman, S. F., Ueno, N. T., Shen, Y., & Babiera, G. (2014, July 1). Underuse of trimodality treatment affects survival for patients with inflammatory breast cancer: An analysis of treatment and survival trends from the National Cancer Database. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. https://pmc.ncbi.nlm.nih.gov/articles/PMC4067942/
