Choice Of Adjuvant Endocrine Therapy In Post
Suggested Adjuvant Endocrine Therapy Approach for Women who are Post-Menopausal at Diagnosis
AI: Aromatase Inhibitor ET: Endocrine Therapy
*High risk disease defined as tumors with lymph node involvement or aggressive histological features. In lymph node negative disease, high risk defined as large tumor size or poor prognosis identified by genomic assays
^ Extended tamoxifen may be appropriate in post-menopausal patients if toxicities or contraindications to AI
Several adjuvant endocrine therapy options are available for post-menopausal women including AI for 5 years, tamoxifen for 5 years , tamoxifen for 2-3 years followed by AI to complete 5 years, tamoxifen for 2-3 years followed by 5 years of AI, tamoxifen for 5 years followed by AI for 5 years. While patient factors and patient preferences should be considered, most guidelines recommend the use of an AI, either for 5 years, or for 2-3 years after prior tamoxifen use if possible . Extended AI therapy may be considered for select women and is discussed below.
Many Women With Early
It turns out that many women with early stage breast cancer dont need chemotherapy. The recent study called the TAILORx trial found that thousands of women with a certain type of early-stage hormone-positive, HER-2 negative breast cancer did just as well with hormone therapy alone. These results will be practice-changing, said Kristen D. Whitaker, MD, a clinical cancer geneticist specializing in breast cancer at Fox Chase Cancer Center.
About 1 in 8 women in the US get invasive breast cancer. Half of these cancers are due to estrogen-sensitive tumors that test negative for the HER2 protein, a protein that promotes the growth of cancer cells.
Breast cancers that test positive for HER2 tend to be more aggressive than other types of breast cancer and are less responsive to hormone therapy alone, which is why patients with this disease are usually treated with a combination of chemotherapy and hormone therapy.
But, patients with cancers that test negative for HER2, have a lower risk of cancer recurrence, and have estrogen-positive cancer in an early stage that hasnt spread to the lymph nodes, may be able to skip chemotherapy and just take hormone therapy alone.
The TAILORx trial found that chemotherapy can be avoided in about 70 percent of women with estrogen sensitive, HER2-negative, lymph node-negative breast cancer, Whitaker said. This is exciting because we now have data to better tailor treatments.
What You Need to Know About Skipping Chemotherapy
Trastuzumab May Also Be Effective For Women With Her2
The protein HER2 plays a role even in breast cancers that would traditionally be categorized as HER2-negative. The drug trastuzumab , which targets HER2, may have an even greater role for treating breast cancer and preventing its spread.
Approximately 20% of women with breast cancer have tumors that are categorized as HER2-positive. Trastuzumab has had a tremendous impact on survival for these women, particularly in the adjuvant setting, after surgery to remove the primary cancer. Patients with HER2-negative breast cancer are not advised to take trastuzumab. However, these new findings have potential implications for an additional 65% of women with breast cancer.
A recent study based on new analyses of old data found that some tumors were incorrectly categorized as HER2-positive, which resulted in those women receiving adjuvant trastuzumab. The women benefited from the treatment as much as did those whose cancer actually was HER2-positive.
We now provide a molecular explanation for the surprising finding that adjuvant Herceptin benefited some women with HER2-negative breast cancer. If this is confirmed in clinical trials, it could alter our approach to breast cancer treatment, said study author Max S. Wicha, MD, of the University of Michigan Comprehensive Cancer Center. Results appear online in Cancer Research .
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B Ovarian Function Suppression With Tamoxifen Or An Aromatase Inhibitor
OFS by surgical or pharmacological means should be considered in high-risk pre-menopausal patients. Surgical OFS via bilateral salpingo-oophorectomy is irreversible and may be a suitable option for women with increased risk of ovarian cancer, and in those who desire permanent OFS. Pharmacological methods are generally reversible and use gonadtropin-releasing hormone agonists such as goserelin and leuprolide to suppress luteinizing hormone and follicle-stimulating hormone and subsequently reducing estrogen production from the ovaries . While initial studies of OFS versus no adjuvant therapy and OFS versus adjuvant chemotherapy failed to demonstrate a reduction in recurrence or death overall , data have suggested that OFS benefits may be observed in younger, pre-menopausal women .
Hormone Receptor Status And Early Breast Cancer Prognosis
Hormone receptor status is related to the risk of breast cancer recurrence.
Hormone receptor-positive tumors have a slightly lower risk of breast cancer recurrence than hormone receptor-negative tumors in the first 5 years after diagnosis .
After about 5 years, this difference begins to decrease and over time, goes away .
For a summary of research studies on hormone receptor status and survival, visit the Breast Cancer Research Studies section.
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Guideline Update Addresses Treatments For Her2
In light of findings from multiple recent clinical trials in HER2-negative metastatic breast cancer, ASCO has revised its treatment recommendations to inform more evidence-based care for metastatic breast cancer.1
This guideline update provides important clinical guidance about the new use of immune checkpoint inhibitors, antibody-drug conjugates, and inhibitors for the treatment of metastatic breast cancer, said Beverly Moy, MD, MPH, of Massachusetts General Hospital Cancer Center, and guideline expert panel Co-Chair. These are important and effective new treatments for breast cancer, and every clinician should be aware of recommendations for optimal usage.
Beverly Moy, MD, MPH
Since 2014, several important new therapies have become available based on robust evidence from numerous clinical trials. They include but are not limited to the BOLERO-6 and PEARL trials for hormone receptorpositive, HER2-negative metastatic breast cancer the ASCENT and EMBRACE trials for triple-negative metastatic breast cancer and the OlympiAD and EMBRACA trials for metastatic breast cancer associated with germline BRCA1/2 mutations. This focused update was developed to address both chemotherapy and targeted therapy for women with advanced, HER2-negative disease that is either endocrine-pretreated or hormone receptornegative.
Following the Evidence
Lisa A. Carey, MD
The Road Ahead
Originally published in ASCO Daily NewsASCO Daily News,
Conflict Of Interest Disclosures
We have read and understood Current Oncologys policy on disclosing conflicts of interest, and we declare the following interests: AAJ has previously provided advisory board services to Roche, Novartis, Pfizer, Eisai, and AstraZeneca, and has received educational meeting travel support from Novartis and AstraZeneca . MG and RF have no conflicts to declare. MJC has previously received meeting support from Amgen and Novartis, and has received educational meeting travel support from Novartis .
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There Are Two Ways To Measure The Her
The most common way to measure the HER-2 status of a potential breast cancer tumor is through an immunohistochemistry test. This will likely be part of an overall histological/pathological evaluation of the tumor.
Various tumor markers, including the HER-2 status indicators, give the pathologist a characterization of the tumor. This helps to predict the future behavior and probable responses, of the tumor to different types of treatments.
The immunohistochemistry test of the HER-2 status measures the over-expression of a particular protein and is typically given a score of 0 to +3.
The pathologist actually counts the number of receptors on the surface of the cancer cells. Indeed, the pathologist can see the cells microscopically because they are receptive to certain protein-based dyes and change color.
Scores of 0 and +1 are indicative of a negative status , whilst +2 and +3 are HER-2 positive . There is no in-between state.
Hormone Receptor Status And Hormone Therapy
Hormone receptor-positive breast cancers can be treated with hormone therapies.
Hormone receptor-negative breast cancers are not treated with hormone therapies because they dont have hormone receptors.
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Monitoring For Potentially Serious Lung Inflammation
The rates of side effects seen with T-DXd and chemotherapy were similar. The most common severe side effects of T-DXd were reduced levels of white and red blood cells and fatigue.
T-DXd can also cause a potentially serious type of lung inflammation called interstitial lung disease. In DESTINY-Breast04, 45 people in the T-DXd group developed this side effect, and 3 died as a result. By contrast, only one person in the chemotherapy group developed this lung condition and it was mild.
Patients receiving T-DXd must be carefully monitored and promptly treated if they develop signs of lung inflammation, Dr. Modi said.
Because oncologists are already using T-DXd to treat some women with breast cancer, they are now more aware of this possible complication and know so much more about how to diagnose it earlier and how to treat it better, said oncologist Patricia LoRusso, D.O., Ph.D., of Yale Cancer Center, who was not involved with the study.
This knowledge, Dr. LoRusso said, has cut the rate of severe interstitial lung disease seen in people treated with T-Dxd since the drug first came into use a few years ago.
The Following Statistics Are A Little Old Now They Are Much Better
There are of course many factors that contribute to the survival of breast cancer. However, some older studies show that only about 60%of patients with HER-2 positive status invasive breast cancer are disease free after 10 years.
In addition, about 65% survive overall .
And, a greater number of HER-2 positive patients succumb to the illness during the first five years than those who are negative for HER-2 overexpression.
At the same time, all other factors assumed to be equal, patients with negative HER-2 status tumors tend to be disease free at a rate of 75% over 10 years and have a slightly higher overall survival rate.
From this, we can informally estimate that women with breast cancer which overexpresses HER-2 are about 10% more likely to have significant difficulties and ultimately succumb to the disease within the first five years, than those who do not.
Because some of the Incidence and Prognosis rates are a little old now check out our brand new Index of Posts on Survival Rates.
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Proteins For Targeted Cancer Drugs
Testing cancer cells for particular proteins can help to show whether targeted drug treatments might work for your breast cancer.
Targeted cancer drugs are treatments that change the way cells work and help the body to control the growth of cancer.
Some breast cancers have large amounts of a protein called HER2 receptor . They are called HER2 positive breast cancers. About 15 out of every 100 women with early breast cancer have HER2 positive cancer.
Targeted cancer drugs such as trastuzumab can work well for this type of breast cancer. These drugs attach to the HER2 protein and stop the cells growing and dividing.
What Does Her2 Positive Mean And How Is It Diagnosed
There are two main tests for HER2 breast cancer:
IHC measures the amount of HER2 proteins on the surface of breast cancer cells. Doctors usually use this method because it gives results quickly.
FISH finds the number of HER2 genes inside the cancer cells. This test may be more accurate, but it is more expensive and takes longer to get results. Doctors often reserve this test for when the results of IHC are unclear.
The test results will tell you the HER2 status, either positive or negative, for the biopsy tissue sample of the tumor. HER2 positive means the test determined that the tumor overexpresses HER2. For IHC testing, you will see one of the following results on the pathology report:
0 or +1: This is HER2-negative breast cancer.
+2: This is an unclear result. It may say equivocal. Retesting with FISH may clarify this result.
+3: This is HER2-positive breast cancer.
If you need FISH testing, the results will look a bit different and more straightforward. You either have a positive or negative result. A positive, or amplified, FISH result means the tumor is HER2 positive.
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Advances In Chemotherapy For Her2
Hirofumi Mukai, Mayuko Ito
Department of Breast and Medical Oncology, National Cancer Center Hospital East , , Japan
Contributions: Conception and design: H Mukai Administrative support: H Mukai Provision of study materials or patients: H Mukai Collection and assembly of data: H Mukai Data analysis and interpretation: H Mukai Manuscript writing: All authors Final approval of manuscript: All authors.
Abstract: Metastatic breast cancer cannot be curable, but significant improvement in overall survival has been observed with the appearance of new agents. The purpose of treatment is to prolong survival and to improve quality of life by reducing cancer-related symptoms. To achieve these goals, individualized approach is required. Chemotherapy is used for patients with hormone receptor negative breast cancer or hormone receptor positive patients who have cancer-related symptoms. The choice of regimen , selection of a specific therapy and the duration of treatment depend on multiple factors, including the tumor burden, general health status, prior treatments and toxicities, and patient preferences.
Keywords: Breast cancer chemotherapy quality of life survival
Submitted Apr 02, 2018. Accepted for publication May 31, 2018.
Overview Of Systemic Therapy Options
The treatment modalities generally employed for early stage HR-positive, HER2-negative breast cancer encompass a combination of definitive local therapy, which includes primary surgical management of the breast and axilla with or without adjuvant radiation, and adjuvant endocrine therapy with or without chemotherapy. The Early Breast Cancer Trialists Collaborative Group analysis of adjuvant chemotherapy in early stage breast cancer demonstrated that the risk of disease recurrence and death is significantly reduced with the use of adjuvant chemotherapy, irrespective of HR status. In addition, adjuvant endocrine therapy is associated with decreased risk of recurrence and death in early stage ER-positive breast cancer . Newer studies incorporating biomarkers have demonstrated that the benefit of chemotherapy is not uniform for all HR-positive breast cancers, and these are discussed in more detail below.
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A Cyclin Dependent Kinase Inhibitors
The role of CDK 4/6 inhibitors is well established as first or second line therapy of metastatic HR-positive breast cancer. There are three CDK 4/6 inhibitors approved by the United States Food and Drug Administration in combination with endocrine therapies for the treatment of HR-positive metastatic breast cancer and both ribociclib and abemaciclib have demonstrated OS benefits . Given the PFS and OS benefits seen in advanced disease, these agents are currently being evaluated in the neoadjuvant, adjuvant and residual disease post neoadjuvant settings in an attempt to reduce the rate of recurrence after definitive treatment for early stage HR-positive disease . The PENELOPE-B study is a phase III study of 13 cycles of palbociclib plus standard endocrine therapy for patients with residual disease after taxane-based neoadjuvant chemotherapy . The PALLAS study is a phase III study assessing the addition of 2 years of palbociclib to 5 years of standard endocrine therapy in stage II-III disease . The MonarchE study is a phase III study of abemaciclib plus standard endocrine therapy in patients with high risk, lymph node positive breast cancer and the NATALEE study is a phase III study of ribociclib plus endocrine therapy in the adjuvant setting . Until the results of these studies are reported, the use of adjuvant CDK 4/6 inhibitors, outside of the clinical trial setting, is not recommended.
Triple Negative Breast Cancer
Triple negative breast cancers don’t have oestrogen receptors, progesterone receptors or HER2 receptors. Around 15 out of 100 women have this type . It is more common in younger women.
Hormone therapies and targeted cancer drugs do not work well for this type of breast cancer. So you are more likely to have chemotherapy.
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Treatments And The Treatment Dilemma
If you have triple negative breast cancer, your doctors will talk with you about chemotherapy. Many patients with triple negative breast cancer are treated with chemotherapy prior to surgery, and patients with stage 2 or 3 triple negative breast cancer may be candidates for immunotherapy combined with chemotherapy prior to surgery.
If you have HER2+ breast cancer but you are negative for hormone receptors, your doctors will talk with you about regimens that combine chemotherapy and HER2-targeted therapy. If your cancer is stage 2 or stage 3, this will likely be given prior to surgery, but if your cancer is stage 1, the HER2-targeted therapy and chemotherapy can be given after surgery.
If your cancer is HER2-negative but hormone receptor positive , you will receive endocrine therapy. Depending on other features of your cancer, your doctor may recommend chemotherapy as well.
When Is Her2 Testing Necessary
Anyone with a new diagnosis of invasive breast cancer should have HER2 testing. Its vital to have this information. It tells your doctor how the cancer is likely to behave and can guide treatment decisions. HER2 testing is a standard part of pathology testing for breast tumors.
You should also have HER2 testing if breast cancer spreads to other parts of the body or returns. This is necessary because it is possible for HER2 status to change. HER2-positive tumors can become negative and vice versa. Again, it is very important to know this for your treatment plan. Your doctor will take a new biopsy sample from the site where the cancer has spread or returned.
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Side Effects Associated With Adjuvant Endocrine Therapy
Although the majority of women will have no or mild symptoms, endocrine therapy can be associated with specific and often bothersome side effects . Both pharmacological and non-pharmacological approaches can help ameliorate these symptoms. As studies have demonstrated an association between side effects and early treatment discontinuation , it is important to educate patients about possible toxicities and encourage them to contact their health care team to discuss possible interventions. Menopausal symptoms such as hot flashes and sweats are seen in 40-60% of patients treated with tamoxifen or AIs, and may be more significant with tamoxifen . Vaginal dryness, vaginal discharge and sexual dysfunction are seen with both tamoxifen and AIs . Weight gain, mood disturbances and fatigue are also commonly observed with both tamoxifen and AIs . AI use is associated with an increased risk of osteopenia/osteoporosis, AI-associated musculoskeletal syndrome , a constellation of symptoms that includes arthralgias, myalgias and stiffness, and is also associated with a potential risk of cardiovascular disease . Tamoxifen increases the risk of thromboembolic disease and endometrial cancer, although the incidence of both toxicities remain low, especially in pre-menopausal women .