Tecentriq For Triple Negative Breast Cancer
Tecentriq is approved for both women and men with breast cancer that is triple negative . The drug is also approved for bladder cancer and stage 3 non-small cell lung cancer when surgery is not possible. While it is still too early to determine the overall survival benefit, findings thus far are encouraging.
Tecentriq is a PD-L1 antibody that works by blocking PD-L1. PD-L1 is a protein that is found on the surface of some cancer cells that prevents the immune system from attacking the cell. Tecentriq blocks PD-L1, essentially taking the mask off of the cancer cell so that the immune system can recognize and then attack the cell.
How Does Immunotherapy Work
Immunotherapy is a type of treatment that uses the bodys own immune system to attack cancer cells.
The immune system works by attacking substances in the body it doesnt recognize. This includes viruses, bacteria, and cancer cells. Cancer cells present a big challenge, because they may not seem very different from normal cells to the immune system. Immunotherapy helps the immune system work better to fight the cancer cells.
Different types of immunotherapy work in different ways. Some types work by boosting your immune system to help it work better. Others give your immune system more tools, such as antibodies, to attack specific cancer cells.
There are four main types of immunotherapy that researchers are studying to treat metastatic breast cancer:
- checkpoint inhibitors
What Is Metastatic Breast Cancer
Metastatic breast cancer is not a specific type of breast cancer. Its the most advanced stage of breast cancer.
Metastatic breast cancer is breast cancer that has spread beyond the breast and nearby lymph nodes to other parts of the body .
Although metastatic breast cancer has spread to another part of the body, its still breast cancer and treated as breast cancer.
For example, breast cancer that has spread to the bones is still breast cancer . Its not the same as cancer that starts in the bone. Breast cancer cells have invaded the bones. So, its treated with breast cancer drugs rather than treatments for cancer that began in the bones.
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Other Types Of Immunotherapy In Breast Cancer
While there are not currently any other immunotherapy drugs approved for breast cancer, a number of methods are being evaluated in clinical trials.
Myths surrounding clinical trials abound, and many people express anxiety about participating. It’s important to keep in mind that every therapy we currently have approved was once studied in a clinical trial.
Breast Cancers Cold Tumor Problem
Our immune system is very complex. Theres a lot of emerging research trying to figure out why some cancers do not respond to immunotherapy,” Dr. Farrington says.
Breast cancer tumors, like many solid tumors affecting other parts of the body, frequently contain few of the immunological cells immunotherapy drugs use when kicking into action. A National Institute of Health study describes these as cold tumors and says cancers that are classically immunologically cold include most breast cancers, as well as glioblastomas, ovarian cancer, prostate cancer and pancreatic cancer.
Breast cancer tumors typically have fewer tumor-infiltrating lymphocytes , such as T-cells, than other cancers. Studies have shown that the larger the concentration of TILs in a breast cancer tumor, the better the prognosis for a positive outcome from treatment.
Many solid tumors such as those found in various breast cancers have immune cells that arent working to kill the tumor cellsin fact, theyre actually feeding them, helping them grow.
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Immunotherapy For Breast Cancer
Immunotherapy is sometimes used to treat locally advanced or metastatic triple-negative breast cancer. Immunotherapy helps to strengthen or restore the immune systems ability to fight cancer. Immunotherapy is sometimes called biological therapy.
You may have immunotherapy to:
- kill breast cancer cells
- stop breast cancer tumours from growing and spreading
- control symptoms of metastatic breast cancer
Your healthcare team will consider your personal needs to plan the drugs, doses and schedules of immunotherapy. You may also receive other treatments.
Monitoring Patients On Treatment
The goal of appropriate monitoring during immunotherapy treatment is to promptly detect immune-related toxicities and intervene before these toxicities cause significant morbidity or mortality. An important principle is to properly educate patients and staff about the symptoms that require prompt reporting to avoid life-threatening complications . The most frequently reported irAEs in breast cancer ICI trials are rash and pruritus , thyroid disorders , and liver function abnormalities . Incidences of irAEs reported in trials of ICI monotherapy or combination regimens for TNBC are summarized in . Particular attention should be paid to new or worsening fatigue, headaches, rash, respiratory symptoms, changes in bowel function, visual changes/eye pain, or musculoskeletal symptoms. Careful monitoring of laboratory studies is also required, including electrolytes, creatinine, glucose, liver function, and thyroid hormone levels.
Reported incidence of irAEs in published ICI clinical trials for metastatic TNBC
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Other Immune Checkpoint Blockades
CTLA-4 is the first immune checkpoint clinically confirmed to be expressed by T cells. It can bind to CD80 and CD86 present on dendritic cells, which restrain the T-cell mediated immune response. There are two main anti-CTLA-4 antibodies: tremelimumab and ipilimumab. In a phase I study of local radiation and tremelimumab in patients with inoperable locally recurrent or metastatic BC, the best response was stable disease, and the median OS was 50.8 months. Moreover, increasing proliferating Treg cells 1-week post-treatment was seen in five patients by peripheral blood mononuclear cell profiles . In a pilot study explore cryoablation with ipilimumab in patients with early stage BC, the results suggested the possibility for induced and synergistic anti-tumor immunity with this strategy . Anti-CTLA-4 combined with radiotherapy appears to be tolerable, thereby, more research is in need to optimize this combination therapy.
Which Cancers Are Treated With Immunotherapy
Immunotherapy drugs have been approved to treat many types of cancer. However, immunotherapy is not yet as widely used as surgery, chemotherapy, or radiation therapy. To learn about whether immunotherapy may be used to treat your cancer, see the PDQ® adult cancer treatment summaries and childhood cancer treatment summaries.
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Qol And Symptom Monitoring
Currently, the majority of experience with immunotherapy for breast cancer has been in the advanced/metastatic setting. Patients with metastatic breast cancer can experience an accumulation of physical symptoms and psychosocial stressors that adversely affect their QOL throughout their continued treatment. Over time, these effects usually become worse as treatment is ongoing. A robust corpus of literature has described key QOL outcomes for patients receiving chemotherapy, radiotherapy, endocrine therapy, or HER2-directed therapies. In addition, throughout a patientâs journey, multiple intrinsic and extrinsic factors may influence QOL, including AEs associated with therapy as well as other characteristics of the individual being treated . However, data are currently lacking on the QOL implications for the addition of ICIs to chemotherapy or other conventional treatments.
Ongoing trials are also evaluating ICIs in early-stage disease. Patients with early-stage breast cancer also experience both physical symptoms and psychosocial stressors that can adversely affect their QOL. Although survivors of early-stage breast cancer generally report high functioning after the conclusion of treatment, important rehabilitation problems may persist beyond 1 year after primary treatment, including difficulties with physical and recreational activities, body image, sexual interest, sexual function, and dating for those who were single.
How Often Do You Receive Immunotherapy
How often and how long you receive immunotherapy depends on:
- your type of cancer and how advanced it is
- the type of immunotherapy you get
- how your body reacts to treatment
You may have treatment every day, week, or month. Some types of immunotherapy given in cycles. A cycle is a period of treatment followed by a period of rest. The rest period gives your body a chance to recover, respond to immunotherapy, and build new healthy cells.
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Is Breast Cancer Immunotherapy Research Continuing
New information about breast cancer immunotherapy is expected in the coming months and years, as more clinical trials are completed. Clinical trials are being conducted across the United States and around the world to evaluate combinations of immunotherapy drugs for the disease. Some studies, like the one mentioned above, combine immunotherapy with chemotherapy or targeted therapy. People with breast cancer are encouraged to participate in immunotherapy clinical trials, whenever appropriate. Although immunotherapy is currently only a standard part of breast cancer treatment for a small number of women with metastatic disease, there is hope that this will change.
What Are The Challenges Of Immunotherapy
One challenge of immunotherapy is not knowing who is likely to benefit from the treatment, as mentioned above. Second, immunotherapy can cause substantial side effects, including life-threatening ones. The most common immunotherapy side effects are skin reactions, such as redness and blistering, and flu-like symptoms, such as fever, nausea, weakness, and body aches. Different types of immunotherapy can cause different side effects. An important third challenge is the high cost of this treatment, which insurance companies may not cover.
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Hormone Therapy For Premenopausal Women
For premenopausal women with metastatic breast cancer, hormone therapy almost always begins with ovarian suppression and either an aromatase inhibitor, tamoxifen or other hormone therapy drug.
Ovarian suppression lowers hormone levels in the body so the tumor cant get the estrogen it needs to grow. This may involve surgery to remove the ovaries or, more often, drugs to stop the ovaries from producing hormones.
Combining ovarian suppression and a hormone therapy drug improves survival over either treatment alone .
If breast cancer progressed during past treatment with a hormone therapy drug, the same hormone therapy drug may not be an option for treatment.
Immunotherapy Gaining Traction As A Treatment For Breast Cancer
Immune system failures are behind many cancers, allowing tumors to grow unchecked. Sometimes the cancer cells may:
- Mimic healthy cells, disguising them from disease-fighting immune cells
- Successfully turn off the bodys natural immune response
- Use immune cells to help them grow
Immunotherapy is a type of treatment developed to overcome such immune system deficiencies.
Getting the immune system to do its job has been particularly difficult when it comes to fighting breast cancer. While immunotherapy has become a promising treatment against many cancers, its only recently gained traction in fighting breast cancer.
Immunotherapy for breast cancer has significantly improved over the last few years. The hard part is waiting for the overall survival data, which takes years, says Laura C. Farrington, DO, Medical Oncologist at Cancer Treatment Centers of America® , Chicago.
The U.S. Food and Drug Administration approved the first breast cancer immunotherapy treatment in March 2019 and a second in November 2020, both for patients with advanced or metastatic triple-negative breast cancer. The treatments are delivered in combination with certain chemotherapy drugs.
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Biomarkers At First Relapse
Genomic instability frequently leads to phenotypic alterations in recurrent tumors compared with the primary site, and therefore repeat biopsy of a metastatic lesion is strongly recommended. Treatment may select for modified marker expression in recurrent tumors and genetic alterations that may also contribute to a metastatic tumorâs ability to spread. Changes in ER/PR and HER2 expression in metastases have been reported at rates ranging from 30% to 40% for ER/PR and 10% to 15% for HER2. Changes in ER, PR, and HER2 status have also been observed after neoadjuvant chemotherapy, with implications for therapy selection in recurrent disease. Similarly, metastases frequently harbor distinct genomic alterations compared with primary tumors, leading to the emergence of new actionable mutations in as many as 24% of patients, including acquired homologous repair deficiency, PI3K mutations, and TMB-H status.
Is There A Future For Immunotherapy In Breast Cancer
Lately, immunotherapytreatment that helps the bodys own immune system fight cancerhas made frequent appearances in news headlines. Indeed, researchers have reported remarkable clinical trial results for a new class of drugs known as immune checkpoint blockade drugs in the treatment of metastatic melanoma, lung, and kidney cancers. Approvals from the U.S. Food and Drug Administration for the drugs Keytruda and Opdivo for melanoma and lung cancer have quickly followed. However, it may be that immunotherapies wont work for all cancers, but only for those considered to be immunogenic that is, cancers that trigger activation of the immune system. Researchers are studying different types of breast cancer to determine whether they are immunogenic, and what that might mean for their prognosis and treatments.
When pathologists examine a biopsy of a tumor, they sometimes notices an accumulation of certain immune system cells within the tumor or in the surrounding normal tissue . The presence of these cells, called tumor-infiltrating lymphocytes , is a rough indication that the tumor has attracted the attention of the immune system, resulting in migration and accumulation of TILs. TILs may signal that immunotherapies could be used to further activate the immune system to destroy the tumor.
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Conflict Of Interest Management
As outlined by IOM standards, all financial relationships of expert panel members that might result in actual, potential, or perceived conflicts of interest were individually reported. Disclosures were made prior to the onset of manuscript development and updated on an annual basis. In addition, panel members were asked to articulate any actual or potential conflicts at all key decision points during guideline development, so that participants would understand all possible influences, biases, and/or the diversity of perspectives on the panel. Although some degree of relationships with outside interests are to be expected among experts, panel candidates with significant financial connections that may compromise their ability to fairly weigh evidence were not eligible to participate in guideline development.
Recognizing that guideline panel members are among the leading experts on the subject matter under consideration and guideline recommendations should have the benefit of their expertise, any identified potential conflicts of interests were managed as outlined in SITCâs disclosure and conflict of interest resolution policies. As noted in these policies, panel members disclosing a real or perceived potential conflict of interest may be permitted to participate in consideration and decision-making of a matter related to that conflict, but only if deemed appropriate after discussion and agreement by the expert panel.
Patterns Of Iraes In Patients With Breast Cancer
In the IMpassion130 trial, a total of 259 patients in the atezolizumab plus nab-paclitaxel group and 183 in the placebo plus nab-paclitaxel group had AEs of special interest that were suggestive of potential immune-related causes. In IMpassion130, the leading cause for atezolizumab discontinuation was peripheral neuropathy. Serious AEs were reported in 105 of 453 patients in the atezolizumab group compared with 81 of 437 patients in the placebo group , and one death due to an AE of special interest was reported in the primary analysis in each arm of the studyâin both cases, hepatitis. On secondary analysis, the AEs of special interest that differed substantially between the atezolizumab group and the placebo group were any-grade rash, hypothyroidism, hyperthyroidism, pneumonitis, and adrenal insufficiency. In KEYNOTE-355, irAEs occurred in 26% of patients in the pembrolizumab plus chemotherapy arm, with 5% of patients experiencing irAEs of grade â¥3. The only irAE of grade â¥3 that occurred in 10 or more patients was skin toxicity . In the immunotherapy group, hypothyroidism and hyperthyroidism occurred in 87 and 15 patients, respectively. Hypothyroidism and hyperthyroidism occurred in 9 and 3 patients in the control group. Management of immune toxicities in other organ systems follows similar recommendations to existing expert panel guidelines. Referral to appropriate specialists for persistent autoimmunity is recommended.
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What Does This Mean For Me
If you have metastatic breast cancer, you will likely first receive a standard of care treatment. The study in this review is very early research. The safety and effectiveness of this treatment for a larger number of patients is not yet known. While this woman responded well and is now living with no evidence of disease , researchers do not know whether her response will be typical, if it will vary between patients, if it was a fluke, or if unintended side effects might occur. It may be some time before we understand who will respond best to this treatment.
This woman was part of an ongoing clinical trial to test this treatment. This trial is enrolling participants who have metastatic breast, ovarian, endometrial or other types of cancer. Patients in this study must have a tumor that can be safely removed. Patients must have tumors that are resistant to standard treatment. If this fits your situation, you may want to consider participating in this trial or in a related study. More information on eligibility for this trial can be found here, or for other trials for metastatic breast cancer at the following link. You can search for open trials with our clinical trial research tool or through ClinicalTrials.gov.
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Management Of Isolated Sites Of Progression On Immunotherapy
The appearance of new lesions while on treatment in the metastatic setting, including immunotherapy, is not necessarily a reason to discontinue therapy. As mentioned above, pseudoprogression may result in the appearance of new lesions which then later decrease in size on subsequent reimaging. There may also be true progression with the appearance of a new solitary lesion . This can occur due to tumor heterogeneity and/or the development of new resistance mechanisms to therapy. In these cases, there may be an isolated site of disease progression in patients who otherwise have a good response to treatment. There is no standard management for these isolated lesions in the setting of otherwise responsive disease.
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