Triple Positive Breast Cancer Treatment Protocol

Treating Aggressive Breast Cancers

Women diagnosed with breast cancer undergo testing to determine the form of the disease and whats driving its growth. This information is key to developing an individualized treatment strategy. Choice of treatment also depends on how extensive the cancer is within the breast, whether it has metastasized, and whether the patient is menopausal.

When either HER2-positive or triple-negative breast cancer is diagnosed early, surgery is often performed to remove the tumor and its surrounding tissue or the entire breast . Nearby lymph nodes sometimes are removed as well.

Neoadjuvant therapy, a treatment given as a first step before the primary treatment, is standard for both HER2-positive and triple-negative breast cancers if the tumor can be surgically removed. Chemotherapy is often used as a neoadjuvant therapy before surgery to shrink the tumor. The goal is to reduce the area that needs to be removed so the surgery can be less extensive, possibly avoiding a mastectomy. For HER2-positive cancer, chemotherapy may be combined with targeted therapy, medication that acts on the specific cause of the cancer.

After neoadjuvant therapy and surgery, the treatment strategies for HER2 and triple-negative breast cancers differ.

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Menstrual Changes And Fertility Issues

For younger women, changes in menstrual periods are a common side effect of chemo. Premature menopause and infertility may occur and could be permanent. If this happens, there is an increased risk of heart disease, bone loss, and osteoporosis. There are medicines that can treat or help prevent bone loss.

Even if your periods stop while you are on chemo, you may still be able to get pregnant. Getting pregnant while on chemo could lead to birth defects and interfere with treatment. If you have not gone through menopause before treatment and are sexually active, its important to discuss using birth control with your doctor. It is not a good idea for women with hormone receptor-positive breast cancer to take hormonal birth control , so its important to talk with both your oncologist and your gynecologist about what options would be best for you. When women have finished treatment , they can safely go on to have children, but it’s not safe to get pregnant while being treated.

If you think you might want to have children after being treated for breast cancer, talk with your doctor soon after being diagnosed and before you start treatment. For some women, adding medicines, like monthly injections with a luteinizing hormone-releasing hormone analog, along with chemo, can help them have a successful pregnancy after cancer treatment. To learn more, see Female Fertility and Cancer.

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, a woman’s menopause status, general health, desire to continue getting treatment, and whether the hormone receptor status and HER2 status have changed on the cancer cells.

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When Is It Possible To Skip Chemotherapy In Breast Cancer Treatment

There are three basic subtypes of breast cancer: hormone receptor-positive, triple-negative, and HER2-positive.

Except for the very smallest cancers in the early stages, when cancer hasnt spread to the lymph nodes, most people with triple-negative and HER2-positive breast cancer require chemotherapy to give them the best chance of not having their cancer return.

In hormone receptor-positive breast cancer, the patients can benefit greatly from anti-estrogen medications, and chemotherapy may have less of a role.

If chemotherapy isnt going to reduce the patients risk of recurrence, then surely one would want to avoid it. Chemotherapy has significant toxicities including, but not limited to:

• low blood counts

Certain Factors Affect Prognosis And Treatment Options

The prognosis and treatment options depend on the following:

• The stage of the cancer .
• The type of breast cancer.
• Estrogen receptor and progesterone receptor levels in the tumor tissue.
• Human epidermal growth factor type 2 receptor levels in the tumor tissue.
• Whether the tumor tissue is triple negative .
• How fast the tumor is growing.
• How likely the tumor is to recur .
• A womans age, general health, and menopausal status .
• Whether the cancer has just been diagnosed or has recurred .

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Ajcc Anatomic And Prognostic Stage Groups

There are three stage group tables for invasive cancer:

• Anatomic Stage Group. The Anatomic Stage Group table is used in regions of the world where tumor grading and/or biomarker testing for ER, PR, and HER2 are not routinely available.
• Clinical Prognostic Stage Group. The Clinical Prognostic Stage Group table is used for all patients in the United States. Patients who have neoadjuvant therapy as their initial treatment should have the clinical prognostic stage and the observed degree of response to treatment recorded, but these patients are not assigned a pathological prognostic stage.
• Pathological Prognostic Stage Group. The Pathological Prognostic Stage Group table is used for all patients in the United States who have surgery as initial treatment and have pathological T and N information reported.

In the United States, cancer registries and clinicians must use the Clinical and Pathological Prognostic Stage Group tables for reporting. It is expected that testing is performed for grade, HER2, ER, and PR status and that results are reported for all cases of invasive cancer in the United States.

AJCC Anatomic Stage Groups

AJCC Prognostic Stage Groups

The Clinical Prognostic Stage is used for clinical classification and staging of patients in the United States with invasive breast cancer. It uses TNM information based on the patients history, physical examination, imaging results , and biopsies.

What Is The Survival Rate Of Triple

According to the American Cancer Society, the 5-year survival rate for localized breast cancer is 99%. For breast cancer with regional spread the survival rate is 86%, and for breast cancer with metastasis is 28%. The overall survival rate for all stages is 90%. This means breast cancer patients are 90% as likely as healthy people to live for at least 5 years after their diagnosis of breast cancer.

In general, the behavior and survival rate for triple-positive breast tumors is similar to ER-positive/HER2-negative tumors. One study in California that looked at nearly 125,000 women with breast cancer found no major difference in survival rates between these types of tumors. Triple-negative tumors, in general, have a shorter survival rate compared to triple positive tumors. With that said, each patient and their cancer is unique. As noted, crosstalk between estrogen receptors and HER2 can lead to treatment resistance to hormonal therapies and HER2-directed treatments, reducing the survival rate.

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Adjuvant Therapy Of Her2

Human epidermal growth factor receptor 2 -positive breast cancer clinical stage T1 N0, confirmed following surgery as pT1 pN0, should receive a de-escalated adjuvant therapy with 12 doses of paclitaxel weekly plus trastuzumab for 1 year . If pathological T or N stage are higher, patients should receive a full-term adjuvant Tz-based regimen or a pertuzumab plus Tz-based regimen . In case of hormone receptor -positive, HER2-positive breast cancer, extended adjuvant treatment with neratinib might be discussed only following a Tz-containing Pz-free adjuvant therapy . In all other cases, if systemic chemotherapy is indicated, patients with HER2-positive breast cancer should receive a full-term Pz plus Tz-based neoadjuvant systemic therapy for 68 cycles . In case of pathological complete response , defined as ypT0/is and ypN0, continuation of the anti-HER2 antibody therapy is recommended up to the completion of 1 year. In patients with pCR and negative lymph nodes before and after neoadjuvant systemic therapy, Tz monotherapy might be sufficient . In patients with lymph node involvement prior to neoadjuvant systemic therapy, dual HER2 blockade with Tz plus Pz is recommended despite pCR . Patients who have residual invasive disease in the breast or lymph nodes following optimal neoadjuvant systemic therapy including a taxane and at least Tz for 9 weeks should receive 14 cycles of trastuzumab emtansine as adjuvant treatment .

Fig. 2.

adjuvant therapy of HER2-positive breast cancer.

Developing A Plan Of Care For Triple

Dr. Pomerenke and a multi-disciplinary team quickly developed a plan of care.

She had what is called a triple-positive cancer, one that is driven by hormones and the HER2 protein, Pomerenke said. That gives us three targets for treatment and these patients can have excellent results with therapy.

Anna was seen in our multidisciplinary clinic, where she met with a medical oncologist, radiation oncologist and support staff all at one visit. This enables us to facilitate treatment and provide the most comprehensive care possible, Pomerenke said.

Without question, there will be bad days after you learn you have cancer. Salvador has surely had them. She wasnt sure she should continue seeking a promotion at work since she didnt feel well. But like many who have received devastating news about their health, she has relied on her daughters, Nadine and Mikaela family, friends and unbreakable faith. Shes also followed her doctors recommendations. A single mom, Salvador has had no choice but resilience.

Daughter Nadine, 24, had earned two bachelors degrees in psychology and linguistics and a masters in linguistics from the University of Colorado and has a job as a clinical research coordinator on the Anschutz Medical Campus. Mikaela, now a senior studying environmental science at Stanford, has been accepted into a masters program at Stanford to study earth systems. Shell travel to the Philippines and Hawaii this summer for internship programs.

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Increased Risk Of Leukemia

Very rarely, certain chemo drugs, such as doxorubicin , can cause diseases of the bone marrow, such as myelodysplastic syndromes or even acute myeloid leukemia, a cancer of white blood cells. If this happens, it is usually within 10 years after treatment. For most women, the benefits of chemo in helping prevent breast cancer from coming back or in extending life are far likely to exceed the risk of this rare but serious complication.

Conflict Of Interest Statement

A. Schneeweiss reports grants from Celgene, Roche, and AbbVie, personal fees from Roche, AstraZeneca, Celgene, Pfizer, Novartis, MSD, Tesaro, and Lilly, and travel grants from Roche and Celgene. I. Bauerfeind reports honoraria from Novartis, Celgene, Pfizer, Roche, GSK, and Lilly. T. Fehm reports honoraria from Daiichi Sankyo, Novartis, Roche, Lilly, MSD, HelloHealthcare, Amgen, AstraZeneca, Pfizer, and Olympus. W. Janni reports grants and personal fees from Amgen, AstraZeneca, Daiichi Sankyo, Lilly, MSD, MSB, Novartis, Pfizer, and Roche. C. Thomssen reports honoraria from Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Lilly, MSD, Mylan, Nanostring, Novartis, Pfizer, Pierre Fabre, Puma, Roche, and Vifor. I. Witzel reports honoraria from Amgen, Celgene, Daiichi Sankyo, Lilly, MSD, Novartis, Pfizer, Roche, and TEVA. A. Wöckel reports personal fees from Amgen, Novartis, Eisai, Celgene, Pfizer, Tesaro, TEVA, Hexal Lilly, Roche, AstraZeneca, Sirtex, MSD, and Genomic Health. V. Müller reports institutional research support from Novartis, Roche, Seattle Genetics, and Genentech, honoraria from Amgen, AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva, Seattle Genetics, Genomic Health, Hexal, Pierre Fabre, Amgen, ClinSol, MSD, Lilly, Tesaro, and Nektar, and travel grants from Roche, Pfizer, and Daiichi Sankyo.

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The Use Of Certain Medicines And Other Factors Decrease The Risk Of Breast Cancer

Anything that decreases your chance of getting a disease is called a protective factor.

Protective factors for breast cancer include the following:

• Taking any of the following:

Patients Can Enter Clinical Trials Before During Or After Starting Their Cancer Treatment

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. Information about clinical trials supported by NCI can be found on NCIs clinical trials search webpage. Clinical trials supported by other organizations can be found on the ClinicalTrials.gov website.

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Starting With Neoadjuvant Therapy

Most often, these cancers are treated with neoadjuvant chemotherapy. For HER2-positive tumors, the targeted drug trastuzumab is given as well, often along with pertuzumab . This may shrink the tumor enough for a woman to have breast-conserving surgery . If the tumor doesnt shrink enough, a mastectomy is done. Nearby lymph nodes will also need to be checked. A sentinel lymph node biopsy is often not an option for stage III cancers, so an axillary lymph node dissection is usually done.

Often, radiation therapy is needed after surgery. If breast reconstruction is planned, it is usually delayed until after radiation therapy is done. For some, additional chemo is given after surgery as well.

After surgery, some women with HER2-positive cancers will be treated with trastuzumab for up to a year. Many women with HER2-positive cancers will be treated first with trastuzumab followed by surgery and then more trastuzumab for up to a year. If after neoadjuvant therapy, any residual cancer is found at the time of surgery, ado-trastuzumab emtansine may be used instead of trastuzumab. It is given every 3 weeks for 14 doses. For women with hormone receptor-positive cancer that is in the lymph nodes, who have completed a year of trastuzumab, the doctor might also recommend additional treatment with an oral targeted drug called neratinib for a year.

Chemo Drugs For Breast Cancer That Has Spread

• Taxanes: Paclitaxel , docetaxel , and albumin-bound paclitaxel
• Antibody drug conjugates

Although drug combinations are often used to treat early breast cancer, advanced breast cancer often is treated with single chemo drugs. Still, some combinations, such as paclitaxel plus gemcitabine, are commonly used to treat metastatic breast cancer.

For cancers that are HER2-positive, one or more drugs that target HER2 may be used with chemo.

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Histopathological Classification Of Breast Cancer

Table 1 describes the histologic classification of breast cancer based on tumor location. Infiltrating or invasive ductal cancer is the most common breast cancerhistologic type and comprises 70% to 80% of all cases.

• Primary lymphoma.

References

Breast Cancer Is Sometimes Caused By Inherited Gene Mutations

The genes in cells carry the hereditary information that is received from a persons parents. Hereditary breast cancer makes up about 5% to 10% of all breast cancer. Some mutated genes related to breast cancer are more common in certain ethnic groups.

Women who have certain gene mutations, such as a BRCA1 or BRCA2 mutation, have an increased risk of breast cancer. These women also have an increased risk of ovarian cancer, and may have an increased risk of other cancers. Men who have a mutated gene related to breast cancer also have an increased risk of breast cancer. For more information, seeMale Breast Cancer Treatment.

There are tests that can detect mutated genes. Thesegenetic tests are sometimes done for members of families with a high risk of cancer. For more information, see Genetics of Breast and Gynecologic Cancers.

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Treatment Of Locally Advanced Or Inflammatory Breast Cancer

For information about the treatments listed below, see the Treatment Option Overview section.

• Targeted therapy .
• Clinical trials testing new anticancer drugs, new drug combinations, and new ways of giving treatment.

Use our clinical trial search to find NCI-supported cancer clinical trials that are accepting patients. You can search for trials based on the type of cancer, the age of the patient, and where the trials are being done. General information about clinical trials is also available.

How To Improve Outlook

Breast cancer is most treatableand curablewhen it’s caught early. The best way to improve your breast cancer prognosis is to get screening mammograms regularly when your healthcare providers suggest and follow up with them about any concerning symptoms.

The less advanced your cancer is when its found, the more accessible treatment is and the better your outlookno matter the subtype.

If youve already been diagnosed with triple-positive breast cancer, consider these steps to improve your outlook:

• Talk to your healthcare provider about what treatments will work for you.
• Find a specialist oncologist who works with triple-positive breast cancers.
• Consider clinical trials of new therapies.
• Know that no two breast cancers are the same.
• Connect with other people with breast cancer through support groups.
• Keep a positive outlook and take care of your mental health.
• Follow a healthy lifestylefor example, eat a nutritious diet and stay active.

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Subtypes Of Breast Cancer

According to the National Cancer Institute’s Surveillance, Epidemiology, and End Result cancer database, the four molecular subtypes of breast cancer are:

• HR-positive/HER2-negative is the most common subtype, accounting for 68% of cases.
• HR-positive/HER2-positive is tied for the second most common, accounting for 10% of cases.
• HR-negative/HER2-negative is tied for the second most common, accounting for 10% of cases.
• HR-negative/HER2-positive accounts for about 4% of breast cancers.

In approximately 7% percent of cases in the NCI database, the subtype is unknown.

Triple-positive breast cancers fall under the HR-positive/HER2-positive subtype, a heterogeneous group of cancers. HR-positive/HER2-positive breast cancer includes cancers that are:

• ER or PR positive
• Have high levels of HER2 or the protein Ki-67

HR-positive/HER2-positive cancers are typically given a higher score that indicates how abnormal cancer cells look in the lab than HR-positive/HER2-negative cancers. They also have worse outcomes.

Triple-positive breast cancer falls under the HR-positive/HER2-positive category because it’s HR-positive and HER2-positive. A small portion of these cancers and triple-positive cancers have some unique features because they have both ER and PR.