Treatment Mechanism Of Action And Outcomes After Brain Metastasis
HER2-targeted monoclonal antibodies
Table presents information on anti-HER2 treatment type by mechanism of action, and disease progression and survival after BM. Four studies evaluated survival among patients receiving a HER2-targeted monoclonal antibody after BM diagnosis and reported that overall survival was longer in patients who received trastuzumab after local therapy compared with patients who did not receive trastuzumab . In Ahn et al. , Berghoff et al. , and Brufsky et al. , the difference in median OS after BM between trastuzumab users and nonusers was 7.8months, 10months, and 13.8months, respectively. Niwinska et al. reported that among patients with HR+ status, trastuzumab users had a 11-month longer median OS compared with nonusers , and among patients with HR- status, trastuzumab users had a 6-month longer median OS compared with nonusers . One study evaluated survival among patients receiving HER2-targeted monoclonal antibody combination therapy and reported that OS was longer in patients who received trastuzumab + pertuzumab compared to those who received other HER2-targeted therapy or no HER2-targeted therapy .
Table 4 Effect of Treatment Mechanisms of Action on Survival, Tumor Response, Time to Progression
HER2-targeted non-monoclonal antibodies
Tyrosine kinase inhibitor combination therapies
Any anti-HER2 therapy
Quality of studies
Table 5 Quality of Studies Included
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Survival Analysis Of Single Hormone Receptor
Approximately 97% of patients with ER + PR- tumors and 88% of patients with ER-PR+ tumors received endocrine therapy. More patients with ER + PR- and ER-PR+ tumors received chemotherapy than the group with ER + PR+ tumors , but less than the group with ER-PR- tumors . Approximately 72% of patients with ER + PR- tumors received both endocrine therapy and chemotherapy, and 24.9% of patients received only endocrine therapy. In ER-PR+ tumors, 80% of patients received both chemotherapy and endocrine therapy, 8.2% of patients received only endocrine therapy and 9.4% of patients received only chemotherapy.
With univariate analysis by Kaplan-Meier method, the survival graph of ER + PR- tumors was located between that of ER + PR+ tumors and ER-PR- tumors. The 5-year and 10-year DFS of ER + PR- tumors was 91.4% and 79.6%, respectively, and the 5-year and 10-year OS was 95.9% and 93.9%, respectively. Patients with ER-PR+ tumors had worse DFS and OS than those with ER + PR-.
Figure 1
Among 1,376 patients with HER2 overexpression, there was no significant difference in DFS between four subgroups , and patients with ER-PR-HER+ tumors had the worst OS . However, the 790 patients who received trastuzumab therapy had similar OS , as did the 586 patients who did not receive trastuzumab therapy .
Figure 2Figure 3Table 2 Multivariate analysis of disease-free survival and overall survival in 1.376 women with HER2-positive breast cancer
Determining Your Her2 Status
A breast biopsy is used to determine HER2 status. The biopsy can be sent for laboratory testing with an immunohistochemistry test. The fluorescence in situ hybridization test looks for the HER2 gene in breast cancer cells.
The results of an immunohistochemistry test show different levels of HER2 positivity. For example, a tumor may be reported as 0, 1+, 2+, or 3+. Tumors with a higher number may be referred to as having an overexpression of HER2.
According to the American Cancer Society, immunohistochemistry test results should be considered as follows:
| Designation | |
|---|---|
| Equivocal | |
| 3+ | HER2-positive |
The impact of being HER2-positive on breast cancer survival is, of course, a top concern. Unfortunately, statistics can be misleading without considering other aspects of your diagnosis, including cancer stage at diagnosis and whether the tumor is also estrogen and/or progesterone receptor-positive.
With this in mind, you may also be tested for progesterone and estrogen receptors. Triple-negative breast cancers are negative for HER2, estrogen, and progesterone, while triple-positive breast cancers are positive for all three.
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From Cured To Stage 4
Others, like Teri Pollastro, a 54-year-old stage 4 patient from Seattle, respond surprisingly well.
Diagnosed with early stage ductal carcinoma in situ in 1999, Pollastro underwent a mastectomy but did not receive chemotherapy, radiation or tamoxifen, since her cancer was ER negative.
âThey used the C-word with me, they told me I was cured,â she said. âEvery time I went back to my oncologist, he would roll his eyes at me when I had questions.â
In 2003, Pollastro switched to Seattle Cancer Care Alliance where she saw Dr. Julie Gralow, a breast cancer oncologist and clinical researcher at Fred Hutchinson Cancer Research Center. Gralow discovered Pollastroâs cancer had metastasized to her liver.
âMy husband and I were in shock,â said Pollastro of her mets diagnosis. âYou donât go from being cured to stage 4.â
Pollastro went on Herceptin, a type of immunotherapy for women with HER2-positive metastatic breast cancer, and did six months of chemotherapy.
âI felt better right away with the treatment,â she said. âBut the problem is, it stopped . Thatâs what you can expect with mets. And thereâs always some residual cancer. And that starts percolating.â
And along with mets, she also had to deal with many misconceptions regarding her disease.
The Mercer Island, Washington, mother of two, who often counsels newly diagnosed patients, sometimes even found it difficult to relate to early stage breast cancer survivors.
Symptoms Of Metastatic Breast Cancer
The symptoms of stage 4 breast cancer depend on the location of the cancer and where it has spread in your body.
- If breast cancer has spread to your bones, you may notice a sudden new bone pain. Breast cancer most commonly spreads to your ribs, spine, pelvis, or arm and leg bones.
- If it has spread to your brain, you may experience headaches, vision or speech changes, or memory problems.
- Breast cancer that has spread to your lungs or liver usually causes no symptoms.
The main treatments for stage 4 breast cancer are targeted drug therapies that destroy cancer cells wherever they are in your body.
These treatments may include:
- hormone therapy, which stops or slows the growth of tumors by preventing your body from producing hormones or interfering with the effect of hormones on breast cancer cells
- chemotherapy, where drugs given orally or through an IV travel through your bloodstream to fight cancer cells
- immunotherapy, which uses drugs that stimulate your immune system to destroy cancer cells
- a combination of these therapies
In some cases, surgery or radiation therapy may be used to treat stage 4 breast cancer.
The following are the common treatment options for different types of stage 4 breast cancer.
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What Are Symptoms Of Triple Negative Breast Cancer
TNBC symptoms are the same as other common breast cancers. And many breast cancer symptoms are similar to other less serious conditions. That means having certain symptom doesnt mean you have breast cancer. Possible breast cancer symptoms include:
- A new lump or mass.
- Swelling in all or part of a breast.
- Dimpled skin.
- Nipple retraction, when your nipple turns inward.
- Nipple or breast skin thats dry, flaking, thickened or red.
- Nipple discharge that is not breast milk.
- Swollen lymph nodes. This symptom happens when breast cancer spreads to the lymph nodes under your arm or near your collarbone.
Regional Relapse Following Breast Cancer Treatment Carries A Poorer Prognosis
Most localized breast cancers are treated by either breast conserving surgery with radiation therapy, or by mastectomy.
A medical study from 2010 estimates that around 40% of all women with breast cancer will suffer a recurrence.
The prognosis following a breast cancer recurrence is influenced by a number of factors. These include:-
- The Disease Free Interval: This is the time elapsed from diagnois and treatment of the first breast cancer to the recurrence
- The location of the recurrence: Whether the recurrence is in the same breast , or if it recurs in the contralateral breast, regional lymph nodes, or the chest wall .
Patients with breast cancer relapses are typically generally treated with either a salvage mastectomy, or radiation to the chest wall, regional lymph nodes, or both.
Systemic therapy may be implemented at this point. However, this will be determined on an individual basis, based on the likelihood of distant metastasis, characteristics of the tumor, and other factors.
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Whats The Difference Between Her2
HER2 proteins can indicate whether breast cancer cells are likely to divide and replicate. HER2-negative breast cancer is more common and means that cancer cells are not producing a lot of HER2.
HER2-positive breast cancer, on the other hand, means that the cells are producing a large number of these hormone receptors, indicating a more aggressive cancer.
- having a history of receiving radiation therapy in your chest area
- smoking or using other tobacco products
Also, while having a family history of breast cancer generally increases your personal risk of breast cancer development, HER2-positive breast cancer is not hereditary.
Study Participants Had Metastatic Or Inoperable Breast Cancer
The clinical trial, called DESTINY-Breast04, enrolled 557 adults who had metastatic or inoperable HER2-low breast cancer and had previously been treated with one or two types of chemotherapy. Nearly 90% of participants had hormone receptorpositive disease, meaning their tumors had receptors for the hormones estrogen and/or progesterone. The trial was funded by the developers of T-DXd, Daiichi Sankyo and AstraZeneca.
Two-thirds of participants were randomly assigned to receive T-DXd and the rest to receive their doctors choice of chemotherapy. T-DXd was given intravenously every 3 weeks and patients were followed for a median of about 18 months.
In the group that received T-DXd, the median time that people lived without their cancer getting worse was about 10 months, compared with 5 months in the chemotherapy group. People who received T-DXd survived for a median of 23.4 months overall, while those in the chemotherapy group survived for a median of 16.8 months.
The numbers were similar when the researchers looked specifically at study participants who had hormone receptorpositive disease.
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What Causes Breast Cancer Recurrence
The goal of cancer treatments is to kill cancer cells. But, cancer cells are tricky. Treatments can reduce tumors so much that tests dont detect their presence. These weakened cells can remain in the body after treatment. Over time, the cells get stronger. They start to grow and multiply again.
Even surgery to remove a cancerous tumor isnt always 100% effective. Cancer cells can move into nearby tissue, lymph nodes or the bloodstream before surgery takes place.
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When Should I Go To The Emergency Room
You might also have unusually strong side effects from your cancer treatment. While your healthcare provider likely gave you medication to help control your side effects, you should go to the emergency room if your side effects continue despite medication.
Many cancer treatments affect your immune system, increasing the chance you will develop infections. Symptoms that might require an emergency room visit during treatment are:
- Fever of 100.5 and above.
- Persistent nausea and vomiting.
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Why Receptor Status Matters
Breast cancer is not a single disease, and researchers now have the ability to break down breast cancer into different subtypes based on the receptor status of the tumors. Among the variations between different types of breast cancers are the proteins found on cell surfaces, which are involved tumor growth. These proteins are related to the genetic material of cancer cells.
For example, with estrogen receptor-positive breast cancer, estrogen binds to specific receptors on breast cancer cells, stimulating proliferation. Similarly, HER2 receptors on the surface of breast cancer cells are stimulated by HER2 protein, promoting the growth and spread of breast cancer.
It’s important to note, however, that all breast cellsboth cancerous and noncanceroushave HER2 receptors on their surfaces. The difference is that HER2-positive breast cancer cells have 40 to 100 times more receptors than HER2-negative breast cancer cells or normal breast cells. In positive cases, the abundance of receptors fuels the cancer.
Breast Cancer Discussion Guide
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Where Do These Numbers Come From
The American Cancer Society relies on information from the Surveillance, Epidemiology, and End Results database, maintained by the National Cancer Institute , to provide survival statistics for different types of cancer.
The SEER database tracks 5-year relative survival rates for breast cancer in the United States, based on how far the cancer has spread. The SEER database, however, does not group cancers by AJCC TNM stages . Instead, it groups cancers into localized, regional, and distant stages:
- Localized: There is no sign that the cancer has spread outside of the breast.
- Regional: The cancer has spread outside the breast to nearby structures or lymph nodes.
- Distant: The cancer has spread to distant parts of the body such as the lungs, liver or bones.
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Drug Combo Lengthens Lifespan Of Women With Common Breast Cancer
The results of a phase-3 clinical trial led by a Stanford researcher showed that two targeted treatments can extend the lifespan and delay the need for chemotherapy in women with a common type of metastatic breast cancer.
George Sledge
Women with a common type of advanced metastatic breast cancer live about nine months longer when hormone therapy is paired with a second drug than do those who receive hormone therapy alone, according to an international, multicenter phase-3 clinical trial led by a researcher at the Stanford University School of Medicine.
The second drug belongs to a class of molecules known as CDK4/6 inhibitors that work to block the division of cancer cells.
Breast cancers are classified according to the presence of specific proteins within or on the surface of tumor cells, and these categories are used to guide treatment decisions. Cancers that express high levels of the estrogen receptor often rely on estrogen to grow and are known as hormone-receptor-positive cancers. The protein HER2, which stands for human epidermal growth factor receptor 2, also is often expressed on cancer cells. When its not, the cancer is known as HER2-negative.
The randomized, double-blind trial enrolled nearly 700 women with hormone-receptor-positive, HER2-negative breast cancers at 142 centers in 19 countries. Prior to enrollment, the women had seen their cancers progress while on endocrine therapy, which is the standard first-line treatment for this type of breast cancer.
Overall Breast Cancer Survival Rate For All Stages Of Breast Cancer
The overall 5 year survival rate for women with breast cancer was 89.7%. That is 89.7 out of 100 women were still alive 5 years after diagnosis, regardless of the stage of the cancer. This figure was taken from the SEERS statistics between the years of 2006 and 2012, so could well be even higher now.
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Breast Cancer : Much Progress But Work Remains
Mention that statistic, and many women in the U.S. immediately know it refers to their lifetime risk of getting breast cancer.
Although the statistic may stir up anxiety, those diagnosed with breast cancer today have a more positive prognosis than ever, experts say. Thats due to better understanding of the disease, wider choices of treatments, and more individualized treatment designed to reduce the risk of recurrence and lessen side effects.
While breast cancer incidence has risen by 0.5% per year in recent years, and it remains the second leading cause of cancer death in women, outpaced only by lung cancer, there are now more than 3.8 million breast cancer survivors in the U.S.
If the disease is caught early, women with breast cancer have a survival rate of an astounding 99%, though that may dip to 28% if the cancer has spread.
But despite the progress, much work remains. Read on to see how far weve come in the fight against breast cancer and what experts say needs to happen next.
Breast Cancer: Not a Single Disease
Breast cancer is increasingly viewed as multiple different diseases, says Harold J. Burstein, MD, a breast oncologist at the Dana-Farber Cancer Institute in Boston.
That discovery, in turn, has helped to individualize treatment and predict exactly how much treatment is needed for a specific patient, he and other experts say.
Molecular Diagnostics and ER-Positive Cancers
New Hope for HER2-Positive Cancers
Expanded Genetic Testing
Mechanisms Of Breast Cancer Metastasis
No one really knows what factors will make a certain patient more or less susceptible to breast cancer metastasis.
There is growing awareness that part of that susceptibility is due to host factors. The host factors are the characteristics of the non-malignant cells and the general biological environment surrounding the malignant breast tumor.
Sometimes the host factors are referred to as the pre-metastatic niche and it is thought that bone-marrow-derived progenitor cells may directly influence the dissemination of malignant cells to distant areas.
Non-neoplastichost cells within the tumor may also play a key role in the regulation of breast cancer metastasis.
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Survival Rates For Breast Cancer
Survival rates can give you an idea of what percentage of people with the same type and stage of cancer are still alive a certain amount of time after they were diagnosed. They cant tell you how long you will live, but they may help give you a better understanding of how likely it is that your treatment will be successful.
Keep in mind that survival rates are estimates and are often based on previous outcomes of large numbers of people who had a specific cancer, but they cant predict what will happen in any particular persons case. These statistics can be confusing and may lead you to have more questions. Talk with your doctor, who is familiar with your situation, about how these numbers may apply to you.