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Er Pr Positive Breast Cancer Treatment

How Is Hormone Therapy Used To Treat Breast Cancer

ER positive, PR positive, HER2 negative in Breast Cancer Treatment – Dr. Nanda Rajaneesh

There are three main ways that hormone therapy is used to treat hormone-sensitive breast cancer:

Adjuvant therapy for early-stage breast cancer:Tamoxifen is FDA approved for adjuvant hormone treatment of premenopausal and postmenopausal women with ER-positive early-stage breast cancer, and the aromatase inhibitorsanastrozole, letrozole, and exemestane are approved for this use in postmenopausal women.

Research has shown that women who receive at least 5 years of adjuvant therapy with tamoxifen after having surgery for early-stage ER-positive breast cancer have reduced risks of breast cancer recurrence, including a new breast cancer in the other breast, and reduced risk of death at 15 years .

Until recently, most women who received adjuvant hormone therapy to reduce the chance of a breast cancer recurrence took tamoxifen every day for 5 years. However, with the introduction of newer hormone therapies , some of which have been compared with tamoxifen in clinical trials, additional approaches to hormone therapy have become common .

Some premenopausal women with early-stage ER-positive breast cancer may have ovarian suppression plus an aromatase inhibitor, which was found to have higher rates of freedom from recurrence than ovarian suppression plus tamoxifen or tamoxifen alone .

Men with early-stage ER-positive breast cancer who receive adjuvant therapy are usually treated first with tamoxifen. Those treated with an aromatase inhibitor usually also take a GnRH agonist.

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.

Hormone Therapy After Surgery For Breast Cancer

After surgery, hormone therapy can be given to reduce the risk of the cancer coming back. Taking an AI, either alone or after tamoxifen, has been shown to work better than taking just tamoxifen for 5 years.

These hormone therapy schedules are known to be helpful for women who are post-menopausal when diagnosed:

  • Tamoxifen for 2 to 3 years, followed by an AI for 2 to 3 years
  • Tamoxifen for 2 to 3 years, followed by an AI for 5 years
  • Tamoxifen for 4½ to 6 years, followed by an AI for 5 years
  • Tamoxifen for 5 to 10 years
  • An AI for 5 to 10 years
  • An AI for 2 to 3 years, followed by tamoxifen for 2 to 3 years
  • For women who are unable to take an AI, tamoxifen for 5 to 10 years is an option

For most post-menopausal women whose cancers are hormone receptor-positive, most doctors recommend taking an AI at some point during adjuvant therapy. Standard treatment is to take these drugs for about 5 years, or to take in sequence with tamoxifen for 5 to 10 years. For women at a higher risk of recurrence, hormone treatment for longer than 5 years may be recommended. Tamoxifen is an option for some women who cannot take an AI. Taking tamoxifen for 10 years is considered more effective than taking it for 5 years, but you and your doctor will decide the best schedule of treatment for you.

These therapy schedules are known to be helpful forwomen who are pre-menopausal when diagnosed:

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What Is Triple Negative Breast Cancer

In addition to being negative for estrogen and progesterone receptors, triple negative breast cancercells also lack a protein known as HER2. Human epidermal growth factor receptor-2 is a protein that promotes cell growth and HER2 positive breast cancers have a higher than normal presence of these proteins, because of mutations in HER2 gene.

Triple negative cancers account for approximately 15% of breast cancers. Triple negative breast cancer more often occurs in African-American women younger than 40, or women who have an inherited mutation in BRCA1 gene, which normally is a tumor suppressor gene, which suppresses cell growth.

What Are The Stages Of Breast Cancer

Challenges in Treating Estrogen Receptor

Breast cancer is staged by the size of the tumor and extent of spread. Breast cancers are also graded from one to three, based on how abnormal the cancer cells look and how fast they grow. One is low grade cancer and three is high grade cancer that grows and spreads rapidly.

The four stages of breast cancer are:

  • Stage I: The tumor is relatively small and localized to the original site, with possible spread to the sentinel lymph nodes, which are the first lymph nodes the cancer is likely to spread to.
  • Stage II: The tumor has grown and spread to a few nearby lymph nodes.
  • Stage III: The tumor has grown into many lymph nodes and other tissue in the breast.
  • Stage IV: The cancer has spread to distant parts of the body.

Another highly detailed classification system is the TNM classification system based on tumor size, lymph node involvement and metastatic spread.

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The Promotion Of A Pro

A novel approach to ER+ mBC treatment was recently published by Lok et al., presenting an idea to attack ER+ mBC via an apoptotic mechanism of BCL2 inhibition . Reminiscent of the renowned Hallmarks of Cancer work by Hanahan et al., their focus promoted apoptosis as the means to maximally reduce the opportunity for further mutations and achieve maximum clinical benefit . In 2000, Perillo et al. showed that BCL2 expression can be upregulated downstream effector molecule during ER stimulation which is significant knowing 30% of ER+ mBC patients possess ESR1-activating mutations . Since then, it has been established that approximately 85% of primary ER+ BC demonstrate BCL2 overexpression .

Important cellular signaling in ER+ BC, drugs either FDA approved or currently under development and their mechanisms of action. Insert shows the detailed mode of action of venetoclax.

What Hormone Receptors Do

Hormone receptors, like other cell receptors, are special proteins found in and on the surface of certain cells throughout the body, including breast cells. These receptor proteins are like the eyes and ears of the cells, receiving messages from hormones and other substances in the bloodstream and then telling the cells what to do. The receptors act like an on-off switch for an activity in the cell. If the right substance comes along that fits into the receptor like a key fitting into a lock the switch is turned on and that particular activity in the cell begins.

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How Is Pr Positive Breast Cancer Treated

One of the main treatments for PR-positive breast cancer is hormone therapy, which keeps HR-positive cancer cells from using hormones to grow. The type you get will depend in part on whether youve gone through menopause yet. Hormone therapy can be part of treatment for any stage of HR-positive breast cancer.

Will I Need Radiation

First-Line ER-Positive Metastatic Breast Cancer Treatments

Most oncologists generally recommend radiation treatment for all people with breast cancer who undergo only removal of the tumor .

For women who undergo whole-breast removal, radiation may be recommended for those who are considered high-risk, especially those with tumors larger than 5 centimeters and with more than four cancerous lymph nodes.

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What Are The Side Effects Of Hormone Therapy

The side effects of hormone therapy depend largely on the specific drug or the type of treatment . The benefits and harms of taking hormone therapy should be carefully weighed for each person. A common switching strategy used for adjuvant therapy, in which patients take tamoxifen for 2 or 3 years, followed by an aromatase inhibitor for 2 or 3 years, may yield the best balance of benefits and harms of these two types of hormone therapy .

Hot flashes, night sweats, and vaginal dryness are common side effects of all hormone therapies. Hormone therapy also may disrupt the menstrual cycle in premenopausal women.

Less common but serious side effects of hormone therapy drugs are listed below.

Tamoxifen

  • breathing problems, including painful breathing, shortness of breath, and cough
  • loss of appetite

Side Effects Of Tamoxifen And Toremifene

The most common side effects of tamoxifen and toremifene are:

  • Vaginal dryness or discharge
  • Changes in the menstrual cycle

When tamoxifen treatment starts, a small number of women with cancer that has spread to the bones might have a tumor flare which can cause bone pain. This usually decreases quickly, but in some rare cases a woman may also develop a high calcium level in the blood that is hard to control. If this happens, the treatment may need to be stopped for a time.

Rare, but more serious side effects are also possible:

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What Are The Symptoms Of Breast Cancer

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

Less Common Types Of Hormone Therapy

ER/PR/Her2 Receptor studies in Breast Cancer

Some other types of hormone therapy that were used more often in the past, but are rarely given now include:

  • Megestrol acetate , a progesterone-like drug
  • Androgens , like testosterone

These might be options if other forms of hormone therapy are no longer working, but they can often cause side effects.

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Can Other Drugs Interfere With Hormone Therapy

Certain drugs, including several commonly prescribed antidepressants , inhibit an enzyme called CYP2D6. This enzyme plays a critical role in the body’s use of tamoxifen because CYP2D6 metabolizes, or breaks down, tamoxifen into molecules, or metabolites, that are much more active than tamoxifen itself.

The possibility that SSRIs might, by inhibiting CYP2D6, slow the metabolism of tamoxifen and reduce its effectiveness is a concern given that as many as one-fourth of breast cancer patients experience clinical depression and may be treated with SSRIs. In addition, SSRIs are sometimes used to treat hot flashes caused by hormone therapy.

Many experts suggest that patients who are taking antidepressants along with tamoxifen should discuss treatment options with their doctors, such as switching from an SSRI that is a potent inhibitor of CYP2D6, such as paroxetine hydrochloride , to one that is a weaker inhibitor, such as sertraline or citalopram , or to an antidepressant that does not inhibit CYP2D6, such as venlafaxine . Or doctors may suggest that their postmenopausal patients take an aromatase inhibitor instead of tamoxifen.

Other medications that inhibit CYP2D6 include the following:

  • quinidine, which is used to treat abnormal heart rhythms

Many Breast Cancer Cases Are Diagnosed After 50

Dr. Torrey explains, “A person’s risk of developing breast cancer increases as they get older. As people age, abnormal changes in their cells are more likely to occur. Breast cancer is most common in females over the age of 50 years. Experts believe that one in eight women who live to age 80 will get the disease. About 77 percent of women are over age 50 at the time they are diagnosed with breast cancer less than 1 percent are diagnosed in their 20s.

The incidence rates for cancer overall climb steadily as age increases, from fewer than 25 cases per 100,000 people in age groups under age 20, to about 350 per 100,000 people among those aged 4549, to more than 1,000 per 100,000 people in age groups 60 years and older.”

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What Is Hormone Therapy

Hormone therapy slows or stops the growth of hormone-sensitive tumors by blocking the bodys ability to produce hormones or by interfering with effects of hormones on breast cancer cells. Tumors that are hormone insensitive do not have hormone receptors and do not respond to hormone therapy.

Hormone therapy for breast cancer should not be confused with menopausal hormone therapy treatment with estrogen alone or in combination with progesterone to help relieve symptoms of menopause. These two types of therapy produce opposite effects: hormone therapy for breast cancer blocks the growth of HR-positive breast cancer, whereas MHT can stimulate the growth of HR-positive breast cancer. For this reason, when a woman taking MHT is diagnosed with HR-positive breast cancer she is usually asked to stop that therapy.

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What To Know About Menopause And Breast Cancer

Optimizing Treatment Options for HER2 / ER Breast Cancer using Models of Endocrine Resistance

Dr. Torrey explains, “After menopause , most estrogen comes from fat tissue. Having more fat tissue after menopause can raise estrogen levels and increase the chances of getting breast cancer, since most POSTmenopausal breast cancers are hormone sensitive and ER/PR positive.”

Dr. Curry-Winchell emphasizes, “Menopause does not cause cancer, but the risk of developing cancer increases as a person ages. A longer exposure to the hormone estrogen increases a woman’s risk of breast cancers. Therefore, people who have been through natural menopause are more likely to develop cancer around as twice as high because of hormonal factors according to a study published in the National Library of Medicine.”

According to the Susan G. Komen organization, “Women who go through menopause later in life have an increased risk of breast cancer compared to women who go through menopause earlier. A pooled analysis of data from 117 studies looked at age at menopause and breast cancer risk. For every year older a woman was when she started going through menopause, breast cancer risk increased by about 3 percent.”

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What Are Hormones And Hormone Receptors

Hormones are substances that function as chemical messengers in the body. They affect the actions of cells and tissues at various locations in the body, often reaching their targets through the bloodstream.

The hormones estrogen and progesterone are produced by the ovaries in premenopausal women and by some other tissues, including fat and skin, in both premenopausal and postmenopausal women and in men. Estrogen promotes the development and maintenance of female sex characteristics and the growth of long bones. Progesterone plays a role in the menstrual cycle and pregnancy.

Estrogen and progesterone also promote the growth of some breast cancers, which are called hormone-sensitive breast cancers. Hormone-sensitive breast cancer cells contain proteins called hormone receptors that become activated when hormones bind to them. The activated receptors cause changes in the expression of specific genes, which can stimulate cell growth.

Breast cancers that lack ERs are called ER negative, and if they lack both ER and PR they may be called HR negative.

Approximately 67%80% of breast cancers in women are ER positive . Approximately 90% of breast cancers in men are ER positive and approximately 80% are PR positive .

Rna Sequencing And Raw Data Processing

MCF7 xenografts treated with hormone pellets were dissociated into single cells, mouse cells were depleted with immunomagnetic beads . For MCF7 xenografts with PGR overexpression, whole glands were sequenced, and mouse and human reads were separated computationally. Raw reads were aligned to the human and mouse genome using HISAT2 , the exact parameters are hisat2 -k 5 -p 4seed 42. Gene counts were generated using FeatureCounts and data preprocessed with the edgeR package from Bioconductor. The Voom function of the limma package from Bioconductor was used to normalize the data for sequencing depth differences, estimate the mean-variance relationship of the log counts, and generate a precision weight for each observation so that data were ready for the limma linear fitting function .

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Treatment For Er Positive Breast Cancer

If your breast cancer is ER positive, you may be offered hormone therapy.

A number of hormone therapies work in different ways to block the effect of oestrogen or reduce the amount of oestrogen in the body.

It may be given to:

  • Reduce the risk of breast cancer coming back after surgery
  • Reduce the size of the cancer or slow down its growth
  • Treat breast cancer that has come back or spread

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Should I Have Breast Reconstruction And When

Figure 5 from HER2

This is another question that has a multi-layered answer. It involves both medical and personal considerations. Some women opt not to have reconstruction. Others believe it benefits their appearance and psychological recovery.

This is another question that has a multi-layered answer. It involves both medical and personal considerations. Some women opt not to have reconstruction. Others believe it benefits their appearance and psychological recovery.

If youre having one or both breasts removed and are considering reconstruction, the stage of your cancer may dictate the timing of the reconstructive surgery. For patients with early-stage breast cancer, Dr. Abraham says immediate reconstruction is reasonable. With a Stage III cancer, you should discuss with your oncologist and surgeon whether immediate reconstruction is advisable.

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Will I Need Surgery And What Kind Should I Have

This is an important question but the answer may be less than definitive. It will vary from patient to patient and you may have more than one choice.

According to the American Cancer Society, most women with breast cancer have some type of surgery. But some breast cancers cant initially be surgically removed. In other cases, whether to operate and the type of surgery may depend on the cancers stage, the tumors size and location, the size of your breast and your personal preference.

In women whose breast cancers are operable, the choices are breast-conserving surgery or mastectomy. Mastectomy is the removal of most or all breast tissue and possibly nearby lymph nodes. Within each of those two broad categories are further options. Talk with your oncologist and breast surgeon. If you have any doubts, you may choose to seek a second opinion.

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