Advanced Cancer That Progresses During Treatment
Treatment for advanced breast cancer can often shrink the cancer or slow its growth , but after a time, it tends to stop working. Further treatment options at this point depend on several factors, including previous treatments, where the cancer is located, and a womans age, general health, and desire to continue getting treatment.
Treatment For Triple Negative Breast Cancer
The main treatments for triple negative breast cancer are surgery, chemotherapy and radiotherapy. The treatment you need depends on:
- where the cancer is
- the size of the cancer and whether it has spread
- how abnormal the cells look under the microscope
- your general health
You might have surgery to remove:
- an area of the breast
- the whole breast
When you have your surgery, the surgeon usually takes out some of the lymph nodes under your arm. They test these nodes to see if they contain cancer cells. The surgeon might check the lymph nodes closest to the breast using a procedure called sentinel lymph node biopsy. Testing the lymph nodes helps to find the stage of the cancer and decide on further treatment.
After breast conserving surgery you usually have radiotherapy to the rest of the breast tissue.
Stage 3a Breast Cancer
If you are diagnosed with Stage 3A breast cancer, it means that one of the following applies to you:
Either:
The tumour is less than 5 cm and breast cancer cells have been found in:
- 4-9 lymph nodes in the armpit. or
- 1 or more lymph nodes under the breastbone
The tumour is larger than 5 cm and breast cancer cells have spread to 1-9 lymph nodes.
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Treating Triple Negative Breast Cancer
Triple negative breast cancer can be treated with a combination of
Research has shown chemotherapy generally has a larger benefit for triple negative breast cancer compared to oestrogen receptor positive breast cancer. Chemotherapy for triple negative breast cancer is often given before surgery. The drugs used are likely to include carboplatin or cisplatin.
Some breast cancer treatments, such as hormone therapy and HER2 targeted therapies are of no benefit to people with triple negative breast cancer.
Receptor Status And Triple Negative Breast Cancer
Your pathology report and your healthcare providers may describe your breast cancer as estrogen receptor , progesterone receptor or human epidermal growth factor receptor-2 positive or negative. Or, they may say that your breast cancer is triple negative or triple positive.
Estrogen and progesterone receptors are proteins found in some cancer cells that allow a hormone to attach and feed the cancer cells. Hormone receptor status is reported as positive or negative and sometimes a percent is also provided. For example, 90% estrogen receptor positive. ER/PR+ breast cancers will, at a minimum, receive some form of hormone therapy such as Tamoxifen.
HER2 is a protein involved in normal cell growth, which may also be present on breast cancer cells. If too much of the HER2 protein is produced, the tumor is considered HER2+ . Breast cancers that are HER2+ will receive HER2 directed therapy such as Herceptin.
Triple positive breast cancer is positive for HER2, ER and PR. You will receive HER2 directed therapies as well as hormone therapy.
Triple negative breast cancer is negative for HER2, ER and PR. Therefore, HER2 directed therapy and hormone therapy are not utilized. Typical treatment is chemotherapy.
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Is Triple Negative Breast Cancer An Aggressive Form Of Cancer
Its true that triple negative breast cancers can grow quickly. But your prognosis or expected outcome depends on more factors than your cancer subtype. Healthcare providers will also consider your tumors size and whether it has spread to your lymph nodes and other parts of your breast. Its also helpful to know researchers are focusing on ways to slow the spread of TNBC.
Do I Need Genetic Counseling And Testing
Your doctor may recommend that you see a genetic counselor. Thats someone who talks to you about any history of cancer in your family to find out if you have a higher risk for getting breast cancer. For example, people of Ashkenazi Jewish heritage have a higher risk of inherited genetic changes that may cause breast cancers, including triple-negative breast cancer. The counselor may recommend that you get a genetic test.
If you have a higher risk of getting breast cancer, your doctor may talk about ways to manage your risk. You may also have a higher risk of getting other cancers such as ovarian cancer, and your family may have a higher risk. Thats something you would talk with the genetic counselor about.
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Where Do These Numbers Come From
The American Cancer Society relies on information from the Surveillance, Epidemiology, and End Results Program 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.
Grading Of Invasive Ductal Carcinoma
In 1957, Bloom and Richardson first developed a histology grading system for invasive ductal carcinoma of the breast, based on the degree of tubule formation, cell nuclear pleomorphism and mitotic count. This system was replaced or modified in 1991 by the Nottingham grading system, which is still based on a points scoring system of the histologic features of the cancer mild, moderate or severe or Grade 1, 2 or 3 .
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Can Tnbc Be Prevented
Researchers dont know all the factors that cause triple negative breast cancer. They have identified the BRAC1 gene mutation as one potential cause for triple negative breast cancer. Unfortunately, you cant prevent BRAC1 because you inherit this gene mutation from your parents.
But there are steps that help prevent breast cancers, including TNBC:
- Maintain a healthy weight.
- Exercise on a regular basis.
- Know your family medical history.
- Monitor your breast health. Studies show 95% of women whose breast cancer was treated before it could spread were alive four years after diagnosis.
- Talk to your healthcare provider about genetic testing for the BRCA gene if you have a family history of breast cancer, ovarian cancer, pancreatic or prostate cancer. If you have the BRCA gene, there are steps you can take to prevent breast cancer.
Tnbc Subtyping And Treatment Regimens
In 2011, Lehmann et al. performed gene expression profiling of tumor samples from 587 TNBC patients and divided TNBC into six subtypes: basal-like 1 , basal-like 2 , mesenchymal , mesenchymal stem-like , immunomodulatory , and luminal androgen receptor . They also performed gene profiling and compared existing TNBC breast cancer cell lines, classifying them into six different subtypes, thus providing an accurate cell model for clinical treatment of TNBC .
Table 1 Genomic TNBC subtypes and assignment of TNBC cell lines to subtypes
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Chemotherapy For Early Tnbc
Early TNBC is treated with chemotherapy. People with TNBC tend to get more treatment benefit from chemotherapy than people with hormone receptor-positive breast cancers do .
Some people get chemotherapy before breast surgery. This is called neoadjuvant chemotherapy.
For people with TNBC who have cancer remaining in their breast after neoadjuvant chemotherapy, treatment with the chemotherapy drug capecitabine may lower the risk of recurrence and improve survival .
Learn more about chemotherapy.
Questionable Issues In Tnbcs
TNBCs are known to metastasize via hematogenous routes and this may be in contradiction with the study of Liu previously mentioned, a study which clearly stated that TNBCs have an active lymphangiogenic process which, normally may favour lymphovascular but not hematogenous dissemination. Currently, the molecular features that differentiate or are able to differentiate lymph node positive TNBCs from lymph node negative TNBCs still remain at a hypothetical level and none of them proved to be useful in the clinical and therapeutic approach of TNBCs patients. But most of the TNBCs cancers have preferentially hematogenous metastases. Besides the high mitotic rate and increased nuclear grade, TNBCs also include pushing border of invasion, frequent tumor necrosis and a large central acellular zone . TNBCs usually exhibit a solid/sheet-like growth pattern and may be associated with an increased lymphocytes infiltrate . Despite the fact that these tumors do not usually metastasize through the lymphatic pathways, TNBCs may be characterized by lymphatic invasion and by an increased LVD . However, not all TNBCs are associated with a poor long term survival, although in a low percentage . EGFR, Src kinase pathway and Cdc42-interacting protein 4 are known to promote TNBCs metastasis . CIP4 inhibition seems to decrease the rate of lung metastasis .
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Age Race Or Ethnicity
Several studies suggest that being premenopausal or of African ancestry increases your risk of developing basal-like or triple-negative breast cancer. Among African-American women who develop breast cancer, there is an estimated 20 to 40 percent chance of the breast cancer being triple-negative. Researchers do not yet understand why premenopausal women and women in some ethnic groups have higher rates of triple-negative breast cancer than other groups of women.
Issues With Current Treatments
According to Dr. Crystal Fancher, the lack of receptors to target mean that some treatments for other forms of breast cancer are not effective for triple-negative breast cancer.
Dr. Fancher is a surgical breast oncologist at the Margie Petersen Breast Center at Providence Saint Johns Health Center and an assistant professor of surgery at Saint Johns Cancer Institute, both in Santa Monica, CA.
Unlike other breast cancers that have hormone receptors, like HER2, triple-negative is harder to treat, she told MNT.
Dr. Jacoub explained that peoples outcomes tend to improve when they use chemotherapy in combination with other treatments. A course of treatment now typically includes immunotherapeutics, which we use before and after surgery as well as during a recurrence, he added.
Platinum chemotherapy, or chemotherapy using platinum-based drugs, is common in the treatment of triple-negative breast cancer due to its effectiveness. However, research has shown that severe side effects can limit its use.
One found around 40 specific side effects, including a decrease in bone marrow production, problems with kidney function, headaches, and other negative effects on the nervous system. There are some treatments available to address these side effects.
Dr. Nan estimated that about 40% of people can use a combination of immunotherapy and chemotherapy.
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Immune Checkpoint Inhibitors For The Im Subtype
Pembrolizumab, a monoclonal anti PD-1, was tested in a phase Ib clinical trial in metastatic PD-L1-positive TNBC. It showed a preliminary ORR of 18.5% in heavily pretreated TNBC . The safety profile of the antibody was very acceptable.
Another anti-PD-L1 antibody, atezolizumab or MPDL3280A, has also shown promising activity in TNBC. In a phase I study with atezolizumab, 21 evaluable patients with metastatic PD-L1-positive TNBC achieved an ORR according to RECIST of 19% . 3 patients with PD-L1-positive TNBC experienced pseudo-progression, continued treatment, and finally demonstrated responses.
Preliminary results of a combination of atezolizumab plus nab-paclitaxel chemotherapy in metastatic TNBC have been reported , and a phase III trial with this combination as first-line therapy in untreated mTNBC has been opened. Multiple additional immune checkpoint receptors and their ligands are prime targets for blockade, such as CTLA-4 . The monoclonal antibody tremelimumab, which inhibits the CTLA-4 pathway, was evaluated in hormone-positive breast cancer and has shown certain activity .
Dr Port Talks Tnbc The Importance Of Finding Cancers Early And More
Theres no one-size-fits-all approach to targeted breast cancer therapies. Breast cancer subtypes all behave differently from each other. We know better therapeutic strategies are desperately needed for triple-negative breast cancer , an aggressive form that lacks targeted therapies, making it especially challenging to treat.
To mark Triple-Negative Breast Cancer Day this year on March 3, we dove deep into the science of TNBC with BCRF investigator Dr. Elisa Port, whose BCRF supported research focuses on this subtype.
Dr. Port is chief of breast surgery of the Mount Sinai Health System and director of the Dubin Breast Center at Mount Sinai Hospital in New York. Dr. Port, BCRF investigator Dr. Hanna Irie, and their teams are working to combat drug resistance in TNBC by developing a drug for the protein PRKCQa promising therapeutic target that may make TNBC more responsive to chemotherapy.
Chris Riback: Dr. Port, thank you for joining. I appreciate your time.
Dr. Elisa Port: Thank you for having me. It’s always a pleasure to be here.
Chris Riback: First, you’re a very well renowned surgeon, of course, and scientific researcher. So obviously it only makes sense that in college, you double majored in Spanish and French. I’m sorry. Dr. Port, did you take a wrong turn when you walked down the stage to get your diploma?
Dr. Elisa Port: Oh my gosh. These are our philosophical questions that if I could answer, I would probably be on the short list for some very big prizes.
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How Is Triple Negative Breast Cancer Diagnosed
The first step might be a mammogram to evaluate a suspicious mass or lump in your breast. Based on what they learn, healthcare providers might perform a biopsy to remove breast tissue. Then they examine the tissues cells to determine the cancer subtype. Identifying the cancer subtype is part of the staging process, which is when providers decide how to treat your cancer.
Sometimes providers use the following tests before treatment to check on your tumors size and whether it has spread, or after treatment to monitor response to treatment:
How Quickly Breast Cancer Develops
You may have heard remarks that cancer has been present for five years before it is diagnosed, and this may sometimes be true.
The actual time it takes for breast cancer to grow from a single cancer cell to a cancerous tumor is unknown, as estimates based on doubling time assume that this is constant throughout the duration of tumor growth.
If doubling time were constant, cancer with a doubling time of 200 days would take 20 years to develop into a detectable tumor, and a doubling time of 100 days would take 10 years to be evident on exam.
In contrast, a breast tumor with a doubling time of 20 days would take only 2 years to develop.
Since the majority of studies have found the average doubling time to be between 50 days and 200 days, its likely that most breast cancers that are diagnosed began at least 5 years earlier .
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Treatment Of Early Tnbc
Early TNBC is aggressive, but it can be treated effectively. Its usually treated with some combination of surgery, radiation therapy, chemotherapy and immunotherapy.
TNBC isnt treated with hormone therapy or HER2-targeted therapy because its ER-negative and HER2-negative.
Learn about emerging areas in drug therapies for early breast cancer.
How Does Staging Relate To Types Of Breast Cancer
In addition to cancer stage, doctors will determine the tumor grade and subtype.
Tumors are graded on a scale of 1 to 3, based on how abnormal the cells appear compared to normal cells. The higher the grade, the more aggressive the cancer, meaning that it tends to be growing quickly.
The subtype is important because treatment and outlook will vary depending on which subtype of breast cancer that you have. Subtypes include:
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Targeted Therapy In Tnbcs
Different potential therapeutic options in TNBCs are summarized in Figure . Unlike the luminal types and the HER2 overexpressing type of breast carcinomas, TNBC lacks a specific targeted therapy. However, considering TNBCs heterogeneity, it is possible that BRCA1/2 mutations, along with AR may represent potential molecular targets in TNBCs treatment . Also, Pim-2, a serin/threonine kinase strongly involved in breast cancer metastasis, may become a therapeutic target in TNBCs . HJ-PI01, a Pim-2 inhibitor, seems to induce autophagic cell death and apoptosis thus decreasing malignant proliferation in TNBC cell lines . Shindikar et al. highlighted the anticancer properties of curcumin and resveratrol in TNBCs treatment, however, difficulties regarding their in vivo availability, distribution and kinetics along with a poor solubility, limits their routine use in patients . Chemotherapeutic agents such as nab-paclitaxel seems to be beneficial in the treatment of aggressive forms of breast cancer, such as TNBCs and HER2+, as well as in elderly and taxane-pretreated women .
What Is Triple Negative Breast Cancer
A diagnosis of triple negative breast cancer means that the three most common types of receptors known to fuel most breast cancer growthestrogen, progesterone, and the HER-2/neu gene are not present in the cancer tumor. This means that the breast cancer cells have tested negative for hormone epidermal growth factor receptor 2 , estrogen receptors , and progesterone receptors .
Since the tumor cells lack the necessary receptors, common treatments like hormone therapy and drugs that target estrogen, progesterone, and HER-2 are ineffective. Using chemotherapy to treat triple negative breast cancer is still an effective option. In fact, triple negative breast cancer may respond even better to chemotherapy in the earlier stages than many other forms of cancer.
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