Executive Summary
The different types of standard treatments for inflammatory breast cancer are explained in detail. Standard treatments are used along with the integration of effective treatment planning. Clinical trials are used as an innovative treatment approach that combines different therapies and drugs for treating inflammatory breast cancer. Chemotherapy, surgery, radiation therapy, HER2 targeted therapy, or hormone therapy are the standard type of treatment used for treating breast cancer. Chemotherapy combinations for inflammatory breast cancer include different combinations of drugs. Inflammatory Breast Cancer Treatments targeting the HER2 receptor and chemotherapy for HER2-positive breast cancer are given. HER2-targeting medications as targeted therapy in inflammatory breast cancer. Pembrolizumab (Keytruda) is an immunotherapy to treat high-risk, early-stage, triple-negative breast cancer combined with chemotherapy before surgery. Hormonal therapy (endocrine therapy) is an effective treatment for Inflammatory Breast Cancer that tests positive for estrogen or progesterone receptors (called ER-positive or PR positive) in all stages of breast cancer. Since inflammatory breast cancer is usually located throughout the breast and the lymphatic vessels in the skin, starting with surgery first may not successfully remove all cancer with negative margins. Reconstructive surgery is used to rebuild the breast in case of inflammatory breast cancer. Newer radiation regimens are used to shorten the length of Inflammatory Breast Cancer treatments from 6 to 7 weeks to 3 to 4 weeks. Palliative care is provided to the patients to cope with mental, physical or financial issues while involving medication, nutritional changes, emotional and spiritual support and other relaxation therapies. Brain metastasis is treated using surgery, radiation therapy, targeted therapy, and immunotherapy. The treatment plan is used in the case of metastatic inflammatory breast cancer, including surgery, targeted therapy, radiation therapy, and immunotherapy, a treatment created to boost the body’s natural defenses to fight the tumor and clinical trial option.
Treatment of Inflammatory Breast Cancer
Standard to care refers to the best-known treatment. In cancer care, different doctors work together to bring out an overall Inflammatory Breast Cancer treatments plan for the patient. This is called a multidisciplinary team.
Treatments recommendations depend on many factors:
- The size, grade and type of tumor
- Whether the tumor is applying pressure on vital parts of the brain
- If the tumor has increased to other parts of the CNS or body
- Possible side effects
- The patient’s preferences and overall health
How Inflammatory Breast cancer is treated
Inflammatory breast cancer is considered locally-advanced breast cancer. It is typically treated with several types of treatment, including chemotherapy, surgery, radiation therapy, HER2 targeted therapy, or hormone therapy, as appropriate 1.
The treatment of inflammatory breast cancer usually starts with chemotherapy. The chemotherapy that takes place before surgery is called preoperative or neoadjuvant therapy. After chemotherapy, patients typically have surgery to remove the breast and receive radiation therapy to the chest wall and lymph nodes. If a patient with stage IV breast cancer metastatic when diagnosed first, the main treatment options are systemic therapies, like chemotherapy. Surgery or radiation therapy are not used commonly.
The types of treatments used for inflammatory breast cancer are mentioned below. The care plan also includes treatment for symptoms and side effects, an essential part of cancer care.
Chemotherapy
Chemotherapy uses medicine to kill or stop the growth of cancerous cells. Depending upon the stage, different chemotherapy is given. The point that makes a difference is how the chemotherapy enters the body and which cells it affects.
Systemic chemotherapy enters the bloodstream to reach cancerous cells all over the body.
Chemotherapy for inflammatory breast cancer that hasn’t increased outside of the breast and regional lymph nodes usually includes a combination of drugs.
Drugs for breast cancer may comprise:
- Capecitabine (Xeloda)
- Carboplatin (available as a generic drug)
- Cisplatin (available as a generic drug)
- Cyclophosphamide (available as a generic drug)
- Docetaxel (Taxotere)
- Doxorubicin (available as a generic drug)
- Pegylated liposomal doxorubicin (Doxil)
- Epirubicin (Ellence)
- Fluorouracil (5-FU)
- Paclitaxel (Taxol)
- Gemcitabine (Gemzar)
- Vinorelbine (Navelbine)
- Eribulin (Halaven)
- Ixabepilone (Ixempra)
- Methotrexate (Rheumatrex, Trexall)
- Protein-bound paclitaxel (Abraxane)
Chemotherapy combinations for inflammatory breast cancer may comprise:
- TAC (docetaxel, doxorubicin, and cyclophosphamide)
- AC or EC (Epirubicin and cyclophosphamide or doxorubicin and cyclophosphamide) followed by T (paclitaxel or docetaxel)
Other chemotherapy combinations that can be used for inflammatory breast cancer are:
- AC (doxorubicin and cyclophosphamide)
- CEF (cyclophosphamide, epirubicin, and 5-FU)
- CMF (cyclophosphamide, methotrexate, and 5-FU)
- CAF (cyclophosphamide, doxorubicin, and 5-FU)
- TC (docetaxel and cyclophosphamide)
- EC (epirubicin and cyclophosphamide)
Inflammatory Breast Cancer Treatments that specifically target the HER2 receptor may be given along with chemotherapy for HER2-positive breast cancer.
The side effects of chemotherapy depend on the person and the drug and dose used. Still, they can include fatigue, nausea and vomiting, risk of infection, numbness and tingling in the fingers and toes, loss of appetite, hair loss, and diarrhoea or constipation. These side effects usually go after treatment ends. Long-term side effects may occur, like nerve damage or fatigue, and, rarely, heart damage or secondary cancers.
Targeted Therapy
Targeted therapy aims at any factor that contributes to the growth and development of cancer cells. It can be a specific protein, gene or tissue environment. These treatments for Inflammatory Breast Cancer are typical and do not harm surrounding cells like those in chemotherapy or Radiotherapy.
All tumors do not have the same target; doctors may recommend testing to understand better changes in the individual tumor’s genes and proteins.
HER2 is a specific protein found on breast cancer cells that controls cancer growth and spread. If inflammatory breast cancer is tested positive for HER2, targeted therapy can be an option for treatment along with standard chemotherapy.
HER2-positive inflammatory breast cancer is treated with drugs that target HER2. As for which HER2-targeted drug to use, the choice depends on cancer’s stage.
Commonly used HER2-targeting medications for breast cancer are
- Trastuzumab (Herceptin, Herzuma, Ogivri, Ontruzant, Hylecta)
- Lapatinib (Tykerb)
- Ado-trastuzumab emtansine (Kadcyla)
- Pertuzumab (Perjeta)
- Neratinib (Nerlynx)
HER2-targeted therapy is usually given along with chemotherapy and then after chemotherapy ends.
Standard combination regimens for HER2-positive inflammatory breast cancer include:
- TCHP (docetaxel, carboplatin, trastuzumab, pertuzumab)
- AC-THP (doxorubicin, cyclophosphamide, paclitaxel, trastuzumab, pertuzumab)
Other combination regimens that may be used for HER2-positive inflammatory breast cancer include:
- TCH (docetaxel, carboplatin, trastuzumab)
- AC-TH (doxorubicin, cyclophosphamide, paclitaxel, trastuzumab)
Suppose a patient has no cancer remaining in the breast at the time of surgery. In that case, they will generally be recommended to continue to receive trastuzumab with or without pertuzumab every three weeks until completion of 1 year of therapy (11 to 14 doses). However, suppose a patient is found to have cancer remaining in the breast at the time of surgery. In that case, they will generally be recommended to receive ado-trastuzumab emtansine every three weeks for 14 doses.
Patients receiving HER2-targeted therapy have a minimal risk of developing heart problems. These chances increase if they also have other risk factors for heart disease. Heart problems don’t always go away, but they are usually treatable with medication.
Immunotherapy
Immunotherapy is also known as biologic therapy. It is designed to boost the body’s natural defenses to fight cancer. It uses substances made either by the body itself or in a laboratory to target, improve, or restore the functioning of the immune system. The drug mentioned below can be used in combination with neoadjuvant chemotherapy to treat inflammatory breast cancer that is triple-negative.
Pembrolizumab (Keytruda). The FDA approves this type of immunotherapy to treat high-risk, early-stage, triple-negative breast cancer combined with chemotherapy before surgery 2. It can be continued to be given alone following surgery.
Different types of immunotherapy can cause various side effects. Common side effects include skin rashes, flu-like symptoms, weight changes, and diarrhoea. Other severe but less common side effects can also occur.
Hormonal therapy
Hormonal therapy (endocrine therapy) is an effective treatment for Inflammatory Breast Cancer that tests positive for estrogen or progesterone receptors (called ER-positive or PR positive) in all stages of breast cancer. Blocking the hormones can possibly slow the growth of cancer and destroy the cancer cells. Hormone therapy is typically advised for hormone receptor-positive cancer after chemotherapy and radiation therapy or metastatic breast cancer treatment 3.
Hormonal therapy is typically taken for at least five years. It may be taken for up to 10 years if there is a higher risk of cancer returning.
Hormonal therapy options include:
- Tamoxifen blocks estrogen from binding to breast cancer cells. It is a hormonal therapy that can be used before or after menopause.
- Aromatase inhibitors (AIs) lowers the amount of estrogen made by the body. These drugs include exemestane (Aromasin), anastrozole (Arimidex), and letrozole (Femara). AIs effectively treat breast cancer in postmenopausal or premenopausal people who are also receiving ovarian suppression.
- Ovarian suppression is the use of surgery or drugs to stop the production of estrogen from ovaries. It may be used in addition to another type of hormonal therapy for people who have not been through menopause. There are two methods used for ovarian suppression:
- Gonadotropin or luteinizing releasing hormone analogues stop the ovaries from producing estrogen. Goserelin (Zoladex) and leuprolide (Eligard, Lupron) are Gonadotropin or luteinizing releasing hormone agonists that pause the ovaries from making estrogen for about 1 to 3 months.
- Surgery performed to remove the ovaries can also stop estrogen production, but this is permanent.
- Fulvestrant (Faslodex) is a drug given with the help of injection once a month and is used to treat metastatic breast cancer 4. It stops estrogen from helping cancer grow in a way that is dissimilar to tamoxifen.
Side effects of hormonal therapy can include hot flashes, body aches and stiffness, decreased sexual desire or ability, and mood swings.
Surgery
Breast cancer surgery involves the removal of the tumor in operation. Surgery is also used to inspect the surrounding axillary or underarm lymph nodes.
Since inflammatory breast cancer is usually located throughout the breast and the lymphatic vessels in the skin, starting with surgery first may not successfully remove all cancer with negative margins. A negative margin means no cancer is left at the edges of the tissue removed during surgery. Any cancer cells left behind during surgery can increase the chances of recurrence in the breast and affect healing. This is why chemotherapy is given first for inflammatory breast cancer to shrink and destroy cancer in the breast, improving the chance that surgery will be successful.
The surgical treatments for inflammatory breast cancer is the removal of the entire breast, a process called mastectomy.
Lymph node removal and analysis
It is crucial to determine whether any of the lymph nodes near the breast contain cancer.
- Sentinel lymph node biopsy – In a sentinel lymph node biopsy, the surgeon finds and removes a small number of lymph nodes from the underarm that receives lymph drainage from the breast. The pathologist examines these lymph nodes for the presence of cancer cells. Generally, a sentinel lymph node biopsy is not appropriate for inflammatory breast cancer and an axillary lymph node dissection.
- Axillary lymph node dissection – The surgeon removes many lymph nodes from the underarm in an axillary lymph node dissection. Then, a pathologist examines these lymph nodes for cancer cells. The actual number of lymph nodes removed can be different for each person. An axillary lymph node dissection is the most preferred way to examine the axillary lymph nodes of the patient with inflammatory breast cancer.
Reconstructive surgery
After a mastectomy, a patient may wish to consider breast reconstruction, surgery to rebuild the breast. A reconstructive plastic surgeon performs breast reconstruction.
There are many ways to reconstruct the breast. It may be done with tissue from another part of the body or with synthetic implants. Specific options may be preferred for inflammatory breast cancer because radiation therapy is almost always needed.
Radiation therapy
Radiation therapy uses high-energy X-rays or particles to destroy cancer cells. The most common radiation treatment type is external-beam radiation therapy, in which radiation is given from the machine outside the body. A radiation therapy schedule consists typically of a specific number of treatments offered over a set period.
Adjuvant radiation therapy is radiation treatment post-surgery. It effectively reduces the possibility of breast cancer returning in both the breast and also the chest wall. For people with inflammatory breast cancer, adjuvant radiation therapy is nearly always recommended after mastectomy due to the high risk of cancer cells remaining in the chest wall.
Standard radiation therapy after a mastectomy is given to the chest wall for five days (Monday through Friday) for 5 to 6 weeks.
Standard radiation therapy after a lumpectomy is external-beam radiation therapy given daily. This includes radiation therapy typically to the whole breast for several weeks, depending on whether cancer had spread to the lymph nodes. A more focused treatment then follows it to where the tumor was located in the breast for the remaining Inflammatory Breast Cancer treatments. This concentrated part of the treatment is called a boost which is standard for people with invasive breast cancer to reduce the risk of a recurrence in the breast.
If there is an indication of cancer in the lymph nodes of the underarm, radiation therapy can be given to the lymph node areas present in the neck or underarm near the breast or chest wall. There has been an interest in newer radiation regimens to shorten the length of Inflammatory Breast Cancer treatments from 6 to 7 weeks to 3 to 4 weeks. However, these have not been studied in patients with inflammatory breast cancer.
Radiation therapy can lead to side effects, including fatigue, swelling of the breast, and skin changes. Skin changes may include discoloration, redness, and pain or burning, sometimes along with blistering or peeling. Seldom, a small portion of the lung can be affected by the radiation, causing pneumonitis (a radiation-related inflammation of the lung tissue). This risk depends on the size and part of the area that received radiation therapy. However, this usually heals with time. In the past, using the older equipment and radiation therapy procedure, people receiving treatment on the left side of the body for breast cancer slightly increased the long-term risk of heart disease. Modern techniques are now able to spare the heart from the effects of radiation therapy.
Palliative care
Managing all of these effects is called supportive or palliative care. An essential part of your child’s care is included with Inflammatory Breast Cancer treatments intended to slow, stop, or eliminate the tumor.
Palliative care includes medication, nutritional changes, emotional and spiritual support and other relaxation therapies.
Palliative care focuses on alleviating how you feel during Inflammatory Breast Cancer treatment by managing symptoms and supporting patients and their families with other non-medical needs. Regardless of type and stage of Cancer age, any person may receive this type of care.
Metastatic inflammatory breast cancer
When cancer starts spreading to other parts of the body, it is called metastatic cancer. Doctors can have different opinions regarding the best standard treatment plan. Clinical trials might also be an option. For many people, the diagnosis of metastatic cancer is very stressful and challenging. It is usually helpful to talk with other patients through a support group or other peer support programs. The treatment plan can include a combination of surgery, targeted therapy, radiation therapy, and immunotherapy, which is a treatment created to boost the body’s natural defenses to fight the tumor.
Remission and the chance of recurrence
When cancer can’t be detected in the body, and there are no symptoms, this is known as remission. This may also be called having ‘no evidence of disease’ or ‘NED.’
A remission can be temporary or permanent. Many people worry about the recurrence of cancer.
If this occurs, a new testing cycle will start again to know as much as possible regarding the recurrence. After this testing is completed, you can discuss the treatment options with your doctor. Mainly, the treatment plan will include the Inflammatory Breast Cancer treatments described above, such as chemotherapy, surgery, and radiation therapy. Still, they may be used in a different combination or given at a different pace. Whichever treatment plan you go for, palliative care will be necessary for relieving symptoms and side effects.
If treatment doesn’t work
Recovery from bone sarcoma is not always possible. If cancer can’t be treated or controlled, it leads to advanced or terminal cancer. It is vital to have straightforward conversations with your health care team to express your feelings, preferences, and concerns. The health care team has unique skills, knowledge, and experience to assist patients and their families. Ensuring that a person is physically comfortable, free from pain, and emotionally supported is extremely important.
References
- 1.Tsai CJ, Li J, Gonzalez-Angulo AM, et al. Outcomes After Multidisciplinary Treatment of Inflammatory Breast Cancer in the Era of Neoadjuvant HER2-directed Therapy. American Journal of Clinical Oncology. Published online June 2015:242-247. doi:10.1097/coc.0b013e3182937921
- 2.Koch RM, Principe DR, Cataneo JL, Rana A. Progress for Immunotherapy in Inflammatory Breast Cancer and Emerging Barriers to Therapeutic Efficacy. Cancers. Published online May 22, 2021:2543. doi:10.3390/cancers13112543
- 3.Masuda H, Brewer TM, Liu DD, et al. Long-term treatment efficacy in primary inflammatory breast cancer by hormonal receptor- and HER2-defined subtypes. Annals of Oncology. Published online February 2014:384-391. doi:10.1093/annonc/mdt525
- 4.Rusz O, Kószó R, Dobi Á, et al. Clinical benefit of fulvestrant monotherapy in the multimodal treatment of hormone receptor and HER2 positive advanced breast cancer: a case series. OTT. Published online September 2018:5459-5463. doi:10.2147/ott.s170736