Nov 15, 2019
In this podcast, Katie Houselog, a certified oncology nurse practitioner with Minnesota Oncology, presented at Ridgeview Medical Center's Live Friday CME Series on October 11, 2019. At this event, updates to metastatic breast cancer was provided.
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Metastatic breast cancer. Three words that most people don't really ever want to hear. But what is happening now with the care of our patients who are surviving with this diagnosis.
Metastatic breast cancer affects about 155,000 Americans. Up to 10% are diagnosed with stage 4, meaning it has spread well outside the breast, to various organs and lymph nodes. Unfortunately even in women who attend their regular mammograms, it may not be detected. 20-30% who initially had earlier stage disease will recur. Young women can be diagnosed, as well as men.
Breast cancer type is important to distinguish, and its important to note that the diagnosis of metastatic disease is not necessarily a death sentence. The NCCN (National Comprehensive Cancer Network) provides guidelines for the care of the various types of breast cancer. Speaking of the types of breast cancer, this can be confusing. There is ER, or estrogen receptor positive and HER2 (or human epidermal growth factor) + or -. In addition, there is also PR or progesterone receptor + or -. The majority however have estrogen receptor + and HER2 - breast cancer. The more + receptors present, the more treatment options there are. Triple negative disease tends to have the worst prognosis (Estrogen, HER2, and Progesterone receptor negative_. There is some promise on the horizon for treatment of this, but the situation still is not great. The 5-year prognosis is just under 30% for metastatic disease sufferers.
The same breast cancer drugs are used regardless of where the tumor has metastasized to. Locations of disease progression varies, and can include the liver, lungs, bones and brain, to name a few.
Treatment options have significantly improved over the years. Hormonal therapy, and the CDK46 inhibitor, which was approved a few years ago, as an example. Targeted immunotherapy is also being used, especially in triple negative cancer. Radiation therapy is used for metastatic breast cancer to help prevent local recurrence or for bone involvement and pain. Supportive care, such as palliation and hospice is also important.
There are a lot of chemotherapeutics, and these can be confusing to the primary care provider and other front line clinicians. Hormonal therapy is give for estrogen receptor + cancer; early stage breast cancer as well. Selective estrogen receptor modulators such as tamoxifen, are used in pre- and post-menopause. Other oral drugs that block estrogen receptors include aromatase inhibitors such as letrozole. LH/RH antagonists, such as Lupron and Zolodex, shut-down the pituitary-gonadal axis. Oophorectomy is also sometimes performed. Estrogen down regulators, such as Fluvestrant, are also used. The CDK46 inhibitors however now stretch out the time to progression of the disease to 27-months from what used to be about a year. Fortunately no significant side effects are seen with this, but neutropenia can happen, although rarely neutropenic fever. Therefore, treatment is continued despite neutropenia with this particular class of drug. If compliance is an issue, the injectable Fluvestrant is preferred over a CDK46 inhibitor.
In women with significant metastases, some up front cytotoxic chemotherapy will sometimes also need to be started in estrogen + patients, followed by hormone therapy. In general, though chemo and endocrinologic therapy is not combined. This is per the ASCO (American Society of Clinical Oncology) guidelines.
Patient "LT" was diagnosed with early breast CA, stage one. T1C, NO MO. She was hormone receptor + times 2 and HER2 -. She was treated with chemotherapy, then tamoxifen and zoledronic acid to prevent osteoporosis. Six years later, she presented with dyspnea. She had significant liver mets. Her CA2729 was markedly elevated. By rights, she should not have recurred. A re-biopsy confirmed the same initial cancer. A CDK46 inhibitor with hormone therapy was given. To prevent fracture in the setting of bone mets, zoledronic acid or denosumab are given. Rarely, osteonecrosis of the jaw can happen with this type of drug.
HER2 + disease represents about 1/3 of patients. The backbone of therapy for this is Herceptin or trasztuzamab. Herceptin and pertuzamab, along with chemotherapy will be given for a newly diagnosed HER2 + case, then a short while later, the chemo will be dropped. For brain metastases, lapatinib with xeloda can be given as well. Cardiac function can be affected by Herceptin and these patients must be followed by cardiology. In the setting of estrogen and HER2 + disease, often a combination of hormonal and HER2 directed therapy used. Sometimes chemotherapy is given first. Although not usual at the same time as the other two. Herceptin and hormonal therapy can be used simultaneously, though.
Immunotherapy, specifically atezolizumab with a chemotherapeutic agent is indicated for metastatic breast cancer, which appears to extend lifespan to 25 months, versus 17 months of chemotherapy alone. This is specifically for triple negative breast cancer. They do need to be PDL 1 +, however, in order to be treated with this. This is tested for through tumor pathology.
Another case, a 19 yo female was diagnosed with metastatic breast CA. She was estrogen + and HER2 -. She went through treatment initially with chemotherapy, then recurred a few years later, and on this recurrence a repeat biopsy result was different. She is not triple -. She was started on chemo and atezolizumab. Her follow-up PET scan showed a + response within about 6 mos.
Immunotherapy is used in a lot of different cancers now: renal, bladder, melanoma, and others. These drugs are check-point inhibitors, which essentially engage out T cells to destroy the cancer cells. In general, some of the more common chemotherapy side effects are not seen with immunotherapy. However, immune side effects can be seen, such as hepatitis, colitis, and thyroiditis. These side effects are treated with a prolonged steroid course. Pembrolizumab can be used in MMR deficient cells, or mismatch repair deficient cancer cells and microsatellite instability high disease (in other words, cells that are prone to mutate). It shows some real promise in women who have previously been treated with other therapies for their cancer and those have been exhausted.
BRAC (or B-R-C-A mutations), can be seen in breast, ovarian and fallopian tube cancers. The platin therapies show good results in this group. Genetic testing and counseling is important for women with breast cancer. As in the case discussed, a woman with significant metastatic disease involving the liver, there was a pseudocirrhosis type clinical picture and the patient demonstrated marked improvement in her liver function and ascites and overall quality of life.
PARP inhibitors are given to help prevent repair of the DNA destruction that happens due to chemotherapy drugs. Essentially, preventing reformation of cancerous cells. These drugs in addition to standard therapy demonstrate improved survival as well.
Next generation sequencing is important as well as it looks at the molecular biology, essentially what attributes a particular type of breast cancer has, and allows us to more adequately target with the various treatment modalities that are available or on the horizon. One downside, however, is that we may be able to pick up mutations that we don't yet have a treatment for.
Monitoring for breast cancer is not purely by the book. There are subjective reasons for monitoring as well, and becomes individualized depending on symptoms, type of disease, cancer marker lab trends as well as response to treatment. Imaging intervals and type of imaging is also somewhat dependent on the patient for these reasons as well.
Breast cancer patients are living longer, and we need to continue to help them an empower them to live as high a quality of life as possible. Various conferences and organizations exist that help our patients continue to cope with and survive their cancer. But, there is also help out there for significant others, friends, and family members who are supporting their loved ones through this difficult time in their life.
A special thanks to Katie for joining us and for all the work she does to help patients suffering with breast cancer. It's important work, and research is ongoing to hopefully one day put an end to this disease. But until then, Katie and others like her continue to take excellent care of these patients by providing them with meaningful treatment as well as hope for a cancer free future!