Sunday, February 25, 2024

Triple Positive Breast Cancer Treatment Protocol

Pyrotinib Os Benefit Confirmed In Her2

Triple-Positive Metastatic Breast Cancer

There were a lot of exciting breastcancer abstracts presented at the San Antonio meeting this month. One of the studies that I found most interesting is the PHOEBE trial. This is a phase III trial which demonstrated that pretreated metastatic HER2-positive breastcancer patients had an improved overall survival when treated with the new agent pyrotinib plus capecitabine as compared to lapatinib plus capecitabine.

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What Is A Hormone Receptor

In breast cancer, hormone receptors are the proteins located in and around breast cells. These receptors signal cells both healthy and cancerous to grow. In the case of breast cancer, the hormone receptors tell the cancer cells to grow uncontrollably, and a tumor results.

Hormone receptors can interact with estrogen or progesterone. Estrogen receptors are the most common. This is why ER-positive is the most common form of breast cancer.

Some people are diagnosed with progesterone receptor-positive breast cancer. The key difference is whether cancerous cells are getting growth signals from estrogen or progesterone.

Testing for hormone receptors is important in treating breast cancer. In some cases, there are no hormone receptors present, so hormone therapy isnt a good treatment option. This is called hormone receptor-negative breast cancer.

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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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Treatment Strategies For Triple

MBC that is positive for both hormone receptors and HER2 is called triple positive. Approximately 10% of MBC is triple positive. Triple-positive MBC is different from hormone receptor-positive or HER2-positive MBC because triple-positive cancer is fueled by both hormone receptors and HER2. The interactions between HER2 and estrogen receptors may lead to resistance to hormone therapy or HER2 targeted therapy.

Read below for more information about triple-positive MBC, current thinking about treatment strategies, and results from a clinical trial testing first-line treatment.

Should I Consider Participating In A Clinical Trial

Breast Cancer Clinical Guidelines

Breast cancer treatment has improved tremendously. The reason for this progress is because patients have been willing to take part in tests of newer treatment options.

For any stage of breast cancer, a well done clinical trial could be your best treatment option, Dr. Abraham says. If you qualify for such a trial, your doctor can answer any questions you may have about participating so that you can determine if its a good fit for you.

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Systemic Treatments For Stage Iv Breast Cancer

Treatment often continues until the cancer starts growing again or until side effects become unacceptable. If this happens, other drugs might be tried. The types of drugs used for stage IV breast cancer depend on the hormone receptor status, the HER2 status of the cancer, and sometimes gene mutations that might be found.

What Is The Treatment For Triple Positive Breast Cancer

In women who have not yet experienced the menopause, oestrogen is produced by the ovaries.

Ovarian ablation or suppression stops the ovaries working and producing oestrogen.

Ablation can be done using surgery or radiotherapy. It permanently stops the ovaries from working and means youll experience the menopause early.

Ovarian suppression involves using a medicine called goserelin, which is a luteinising hormone-releasing hormone agonist .

Your periods will stop while youre taking it, although they should start again once your treatment is complete.

If youre approaching the menopause , your periods may not start again after you stop taking goserelin.

Goserelin comes as an injection you have once a month.

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What Is Her2 And What Does It Mean

HER2 is a protein that helps breast cancer cells grow quickly. Breast cancer cells with higher than normal levels of HER2 are called HER2-positive. These cancers tend to grow and spread faster than breast cancers that are HER2-negative, but are much more likely to respond to treatment with drugs that target the HER2 protein.

All invasive breast cancers should be tested for HER2 either on the biopsy sample or when the tumor is removed with surgery.

Eliminating Surgery Or Radiotherapy After Systemic Therapy In Treating Patients With Her2 Positive Or Triple Negative Breast Cancer

Chemotherapy Options for Triple Negative Breast Cancer
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
First Posted : October 26, 2016Last Update Posted : September 28, 2022
Condition or disease

Intervention/treatment Phase
Estrogen Receptor NegativeHER2 Positive Breast CarcinomaHER2/Neu NegativeInvasive Breast CarcinomaProgesterone Receptor NegativeStage I Breast Cancer AJCC v7Stage IA Breast Cancer AJCC v7Stage IB Breast Cancer AJCC v7Stage II Breast Cancer AJCC v6 and v7Stage IIA Breast Cancer AJCC v6 and v7Stage IIB Breast Cancer AJCC v6 and v7Triple-Negative Breast Carcinoma Radiation: External Beam Radiation TherapyOther: Laboratory Biomarker AnalysisOther: Quality-of-Life AssessmentOther: Questionnaire AdministrationRadiation: Whole Breast Irradiation Not Applicable


I. To determine the 6 months , 1, 2, 3, and 5-year biopsy confirmed ipsilateral breast tumor recurrence rate among patients who do not undergo surgery .

II. To determine the pCR rate 6 months after radiation therapy based on image- guided biopsy .



Cohort B Radiation:

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Her2 Breast Cancer Treatment

Targeted therapy is the hallmark of treatment for HER2-positive cancer. The drug used most often is trastuzumab . Trastuzumab interferes with HER2 production and slows or prevents the cancer cells from growing. It is often administered with the chemotherapy agent emtansine in a combined drug called T-DM1.

Another medication, pertuzumab , is sometimes prescribed with trastuzumab when the cancer has spread to other parts of the body or metastasized. Oncologists also may prescribe an aromatase inhibitor, such as lapatinib or neratinib to lower estrogen levels.

If the cancer is also HR-positive, oncologists often prescribe endocrine therapy after the completion of targeted therapy. Endocrine or hormone therapy helps prevent cancer from returning by suppressing estrogen production. Tamoxifen is a common form of endocrine therapy used primarily in premenopausal women. It belongs to a class of drugs called selective estrogen receptor modulators .

Postmenopausal women have the option instead of taking an aromatase inhibitor , such as anastrozole , exemestane , or letrozole to block estrogen production. Postmenopausal women who have completed a tamoxifen regimen may be encouraged to follow up with an AI for added benefit.

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Pathologic Response To Neoadjuvant Chemotherapy

Overall, 30 of 85 patients’ tumors showed pCR following neoadjuvant chemotherapy. In the group of patients who were node pretreatment node-positive, 28 of 50 were downstaged to N0 following chemotherapy. pCR was significantly associated with Nottingham grade: 50% of grade 3 tumors showed complete response versus 21% of grade 2 tumors . pCR was significantly more frequent for patients whose tumors showed 3+ IHC staining than for those with tumors with 0 to 2+ IHC staining and HER2 amplification by FISH . Among the 36 tumors with pretreatment HER2 FISH assessments, neither the mean HER2/CEP17 ratio nor the mean HER2 signals per cell were significantly different between cases that achieved pCR and those that did not . The degree of ER and PR expression was not significantly associated with response to therapy. The mean ER H-score for tumors with pCR was 212.93, versus 219.02 for those that did not achieve pCR , and the mean PR H-score was also not significantly different between the groups . These values were also not significant when comparing ER and PR H-scores with RCB continuous values.

HER2 IHC was the only significant predictor for pCR by both univariate and multivariate logistic regression analyses . Histologic grade was associated with improved pCR on univariate but not multivariate analysis, whereas ER H-score and PR H-score did not correlate with pCR.

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Relationship Between Hormone Receptor And Her2 Results Before Neoadjuvant Chemotherapy

The results of hormone receptor expression compared with HER2 IHC results are summarized in Table 2. Neither the expression of ER nor that of PR by H-score correlated with HER2 IHC expression , HER2 FISH ratio , or HER2 signals per cell . Further, cases that showed either high expression or low expression of both ER and PR also did not show a significant correlation with HER2 staining, FISH ratio, or HER2 signals per cell.

How Do Oncologists Determine Whether Someone Can Skip Chemotherapy

Breast Cancer Tissue Markers, Genomic Profiling, and Other Prognostic ...

Several factors are used to determine the need for chemotherapy for early stage breast cancer. The size of the cancer and whether the cancer has spread to the lymph nodes are two of the clinical features that are used.

Hormone receptor status is also a strong determinant of the need for chemotherapy. While many people with HER2-positive and triple-negative breast cancer do require chemotherapy, we can safely avoid chemotherapy in some people with hormone receptor-positive breast cancer.

The Oncotype DX test analyzes genes in cancer cells to help determine whether cancer will spread or reappear, and whether chemotherapy is needed in addition to anti-estrogen medications to reduce the chance of cancer spreading or returning.

You may be eligible for the Oncotype DX Breast Recurrence Score test if you have early stage, estrogen receptor-positive , or HER2-negative breast cancer. This test is a huge advance because it does allow many people with this subtype of breast cancer to skip chemotherapy.

In ER-positive breast cancer, if the Oncotype DX is in the range where there isnt a chemotherapy benefit, anti-estrogen medications will be used to reduce the risk of recurrence. These medications include aromatase inhibitors and tamoxifen.

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Clinical Features And Treatment

The study included 85 patients with a median age of 47 years at the time of diagnosis . The mean clinical tumor size at presentation was 3 cm , with 83.5% of patients having at least clinical T2 tumors. Four patients presented with inflammatory carcinoma. Fifty patients were clinically node-positive and/or had biopsy-proven nodal metastasis before chemotherapy. Most patients received AC-THP as the neoadjuvant regimen. Fifty-two patients underwent mastectomy and 33 had breast-conserving surgery.

Clinical and Histomorphologic Features of Studied Patients and Hormone Receptor and HER2 Results Determined in Pretreatment Core Biopsies

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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Er And Pr Immunohistochemical Staining Results Before Neoadjuvant Chemotherapy

TPBCs showed high expression of ER in 63.5% of cases as assessed by H-score . High expression of PR was observed in 38.8% of cases. Twenty-seven of the 85 tumors showed high expression of both ER and PR , while 8 showed low expression of both hormone receptors. The median H-scores for ER and PR were 270 and 150 , respectively.

What Are The Symptoms Of Breast Cancer

Triple positive breast cancer patient doing well after treatment by Loyolas multidisciplinary team

The most common symptom of most breast cancers is a lump in the breast. A painless, hard mass with irregular edges is most likely cancer, but breast cancers can also have a lump that is soft and tender to the touch. Other possible symptoms in the first three stages of breast cancer include:

  • Change in the size and shape of the breast
  • Asymmetry in the breast compared to the other
  • Skin dimpling or other abnormal changes in the breastâs skin

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Her2 Immunohistochemical Staining And Her2 Fish Results Before Neoadjuvant Chemotherapy

Fifty-two tumors showed 3+ staining, 28 showed 2+ staining, and 5 showed 0/1+ staining . FISH was performed in 36 cases including 4 cases that showed 3+ HER2 IHC staining. The mean FISH HER2/CEP17 ratio for all tumors studied was 3.6 and the mean HER2 signals per cell was 8 . Sixteen tumors showed low amplification defined as HER2/CEP17 ratio of 2 or greater and 4 to 6 HER2 signals per cell, which included 14 tumors with 2+ staining and 2 with 0/1+ staining. No tumors showed other nonclassical FISH results such as monosomy-like or coamplification/polysomy.

Is Hormone Therapy Effective For Triple

Triple positive breast tumors are both ER and PR positive. Therefore, hormone or endocrine therapy is effective against these types of breast cancer cells. Hormonal drugs prevent estrogen and progesterone hormones from attaching to the ER and PR receptors on the cancer cells. Thus, hormone therapy can reach cancer cells anywhere in the body, not just in the breast. However, it is ineffective against tumors that dont have hormone receptors, such as triple-negative breast cancers.

It is worth noting that triple-positive cancers can behave differently from ER-positive or HER2-positive cancers alone. For example, there can be crosstalk between the receptors, making hormone therapy, such as anti-estrogen therapy, less effective in triple-positive tumors. Similarly, crosstalk between the receptors can make triple-positive breast cancers resistant to HER2-targeted therapy.

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Other Types Of Breast Cancer

There are some other less common types of invasive breast cancer.

Invasive lobular breast cancer

About 1 in 10 invasive breast cancers start in the lobes of the breast. This type can sometimes be difficult to diagnose on a mammogrambecause of the way it grows. Some women may need an MRI scan.

Inflammatory breast cancer

This is when cancer cells grow along and block the tiny channels in the skin of the breast. The breast then becomes inflamed and swollen. Inflammatory breast cancer is rare.

Pagets disease of the breast

This is a condition that causes a red, scaly rash on the skin of the nipple. Women with Pagets disease of the breast may have DCIS or invasive breast cancer.

Finding The Right Balance Of Treatment

Eliminating the breast cancer surgery paradigm after neoadjuvant ...

“Triple-positive” refers to breast tumors that are ER-, PR- and HER2-positive. It means the cancer cells grow in response to estrogen , progesterone and a growth-promoting protein that’s on the outside of all breast cells known as HER2. These cancers tend to grow and spread quickly but are very responsive to medical treatment. In Carol’s case, the tumor was small , but cancer had spread to a lymph node.

“Because of my age and cancer type I was 29 in 2015 when this all began Dr. Dormady and I opted for the whole shebang,” says Carol. “Two weeks after I gave birth, we started with targeted chemotherapy.” That included four rounds of Adriamycin and Cytoxan followed by 12 rounds of Taxol and 12 months of Herceptin.

Dr. Shyamali Singhal performed the lumpectomy, which was followed by radiation treatment with Dr. Robert Sinha. “I am now on my last year of five years of hormone treatment with Arimidex to lower my estrogen levels,” says Carol.

When asked if she built in any time for emotional and psychological therapy, she says, “Staying at home with a new healthy, happy baby. That was therapy.” All told, Carol would end up taking a year and a half off from work to concentrate on recovery.

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Tests On Your Breast Cancer Cells

After a biopsy or surgery to remove breast tissue, a sample of cells is sent to the laboratory. A doctor called a pathologist does various tests on the cells. This can diagnose cancer and also show which type of cancer it is.

Some tests can also show how well particular treatments might work, such as hormone therapies or targeted cancer drugs.

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.

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