Thursday, July 18, 2024

Hormone Receptive Breast Cancer Treatment

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Is Estrogen A Risk Factor For Breast Cancer

Updates on hormone receptor-positive HER2-negative breast cancer

Studies have also shown that a womans risk of breast cancer is related to the estrogen and progesterone made by her ovaries . Being exposed for a long time and/or to high levels of these hormones has been linked to an increased risk of breast cancer. Increases in exposure can be caused by starting menstruation early, going through menopause late, being older at first pregnancy, and never having given birth. Conversely, having given birth is a protective factor for breast cancer.

Palbociclib In Combination With Aromatase Inhibitors

PALOMA-1 is the first randomized phase 2 study comparing the efficacy and safety of palbociclib plus letrozole versus placebo plus letrozole .One hundred sixty-five patients from 12 countries were randomly assigned to the palbociclib plus letrozole group and the letrozole group .PALOMA-1 final results displayed that palbociclib combined with letrozole has a significantly improved progression-free survival than letrozole alone in postmenopausal women with no prior treatment.Table 1 shows the detailed information about enrolled patients in trials.

Moreover, the phase 3 PALOMA-2 trial with randomized 2:1 was used to evaluate the findings of PALOMA-2.PALOMA-2 results confirmed palbociclib combined with letrozole has a significantly longer PFS than that with letrozole alone , with a higher incidence of adverse events in the palbociclib group .Palbociclib to letrozole maintains the health-related quality of life and has a better pain score than the placebo group .

Recently, a randomized, double-blind, phase 3 AMEERA-5 trial was ongoing, and 415 patients were enrolled to evaluate the efficacy and safety of amcenestrant in combination with palbociclib first-line therapy in advanced breast cancer with ER+/HER2- .

What Types Of Hormone Therapy Are Used For Breast Cancer

Several strategies are used to treat hormone-sensitive breast cancer:

Blocking ovarian function: Because the ovaries are the main source of estrogen in premenopausal women, estrogen levels in these women can be reduced by eliminating or suppressing ovarian function. Blocking ovarian function is called ovarian ablation.

Ovarian ablation can be done surgically in an operation to remove the ovaries or by treatment with radiation. This type of ovarian ablation is usually permanent.

Alternatively, ovarian function can be suppressed temporarily by treatment with drugs called gonadotropin-releasing hormone agonists, which are also known as luteinizing hormone-releasing hormone agonists. By mimicking GnRH, these medicines interfere with signals that stimulate the ovaries to produce estrogen.

Estrogen and progesterone production in premenopausal women. Drawing shows that in premenopausal women, estrogen and progesterone production by the ovaries is regulated by luteinizing hormone and luteinizing hormone-releasing hormone . The hypothalamus releases LHRH, which then causes the pituitary gland to make and secrete LH and follicle-stimulating hormone . LH and FSH cause the ovaries to make estrogen and progesterone, which act on the endometrium .

Examples of ovarian suppression drugs are goserelin and leuprolide .

Blocking estrogens effects: Several types of drugs interfere with estrogens ability to stimulate the growth of breast cancer cells:

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How Long Does It Take For Hrt To Cause Cancer

Most types of HRT increase the risk of breast cancer. But the risk is higher for those using combined HRT, which uses both oestrogen and progestogen. Vaginal oestrogens are not linked to an increased risk of breast cancer, whereas tibolone is. Taking HRT for 1 year or less only slightly increases breast cancer risk.

Types Of Hormone Receptors

Challenges in Treating Estrogen Receptor
  • There are two types of receptors, estrogen, and progesterone.
  • If your tumor has estrogen receptors, it is called estrogen receptor-positive or ER+.
  • If your tumor has progesterone receptors, it is progesterone receptor positive or PR+.
  • Your tumor can be positive for one or both hormone receptors. This may be written ER/PR+, ER+/PR-, ER-/PR+.
  • HR+ breast cancer can also be HER2 positive.

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When Are Hormone Blockers Used

Hormone inhibitors and blocker options may depend on a persons stage of life.

  • Hormone inhibitors are only used in postmenopausal women. They can be given to premenopausal women if steps are taken by the treatment team to put the ovaries to sleep by blocking the ovaries from producing estrogen or progesterone.
  • Hormonal therapy may also be called anti-hormone treatment. Think of it as the opposite of hormone replacement therapy . If pathology tests show that the tumor in your breast has hormone receptors , then hormonal therapy may be recommended for you after the completion of your acute treatment .
  • Hormonal therapy keeps breast cancer cells from receiving or using the natural female hormones in your body which they need to grow. Hormonal therapy also blocks the ability of health breast cells to receive hormones that could stimulate breast cancer cells to regrow again in the form of recurrence of the breast cancer within the breast or elsewhere in the body.

Selective Er Modulators And Down

Tamoxifen is the drug most extensively used when an ET is required, both in pre- and postmenopausal women, and is still considered the SERM of choice. TAM 1A) was initially studied as anti-fertility drug, demonstrating soon favorable effects in patients with ER+ BC, as well as on bone tissue and cardiovascular system. TAM acts as a partial nonsteroidal agonist in some tissues, such as liver, uterus and bone, but is a competitive receptor inhibitor in the breast and brain. In these tissues, TAM selectively blocks signaling at the level of ERs, also inhibiting the proliferation of ductal cells. TAM is hydroxylated by the cytochrome P450 enzyme system into 4-hydroxy tamoxifen , and further metabolized in the liver, thanks to a CYP2D6-mediated oxidation, to endoxifen . Endoxifen and 4HT are the main active metabolites of TAM, exhibit similar ability in binding to ERs, and are more potent than TAM in suppressing estrogen-dependent cancer cells. The relationship between CYP2D6, endoxifen or 4HT serum levels and the response to TAM therapy has long been studied, but the hypothesized role of CYP2D6 genotype as prognostic factor affecting recurrence in patients with BC was not confirmed. However, CYP2D6 inhibitors, such as antipsychotic drugs, selective serotonin reuptake inhibitors , and some cardiac medications have the potential to affect response to SERM therapy.

Chemical structures of the main selective estrogen receptor modulators.

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Breast Cancer And Tamoxifen

Tamoxifen is a pill that doctors have prescribed for more than 30 years to treat breast cancer. It works by keeping estrogen from attaching to the cancer cells.

Doctors first used tamoxifen to treat women whose breast cancer had spread in their bodies because it slowed or stopped the growth of the disease. The drug also lowers the chance that some early stage breast cancers will come back. And it can lower the risk that a woman will get cancer in the other breast later on.

Women who are at high risk for breast cancer can take tamoxifen to try to lower their chances of getting the disease. Itâs an alternative to watchful waiting or having surgery to remove a breast, called a mastectomy, before they get the disease.

Tamoxifen is an option for:

  • Treatment of the earliest form of breast cancer, ductal carcinoma in situ , along with surgery
  • Treatment of abnormal cells in the glands that make milk, called lobular carcinoma in situ , to lessen the chance that theyâll become more advanced breast cancer
  • Treatment of breast cancer in men and women whose cancers use estrogen
  • Treatment of breast cancer that has spread to other parts of the body or that comes back after treatment
  • To prevent breast cancer in women at high risk for the disease

Some people should not use tamoxifen:

Talk to your doctor to see if tamoxifen is right for you.

What Are Estrogen And Progesterone Receptors

Advancements in Estrogen ReceptorPositive Breast Cancer

Receptors are proteins in or on cells that can attach to certain substances in the blood. Normal breast cells and some breast cancer cells have receptors that attach to the hormones estrogen and progesterone, and need these hormones for the cells to grow.

Breast cancer cells may have one, both, or none of these receptors.

  • ER-positive: Breast cancers that have estrogen receptors are called ER-positive cancers.
  • PR-positive: Breast cancers with progesterone receptors are called PR-positive cancers.
  • Hormone receptor-positive: If the cancer cell has one or both of the receptors above, the term hormone-receptive positive breast cancer may be used.
  • Hormone receptor-negative: If the cancer cell does not have the estrogen or the progesterone receptor, it’s called hormone-receptor negative .

Keeping the hormones estrogen and progesterone from attaching to the receptors can help keep the cancer from growing and spreading. There are drugs that can be used to do this.

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Estrogen And Progesterone Receptor Testing For Breast Cancer

To help doctors give their patients the best possible care, the American Society of Clinical Oncology and the College of American Pathologists developed evidence-based guidelines to improve the accuracy of testing for estrogen and progesterone receptors for breast cancer. This guide for patients is based on ASCO’s and CAP’s 2020 updated recommendations.

Questions To Ask Your Doctor

To learn more about estrogen and progesterone receptor testing for breast cancer, consider asking your doctor the following questions:

  • What are the results of the ER and PR tests on my tumor sample? What do they mean?

  • Does this laboratory meet the standard guidelines like those from ASCO and the CAP?

  • Has a board-certified pathologist diagnosed my cancer?

  • Do you know if this is an experienced lab and if my tissue was quickly given to the pathologist after my biopsy or surgery, as recommended by guidelines?

  • Can I obtain a copy of my pathology report ?

  • Is my ER and PR status indicated on the pathology report? Was the ASCO-CAP guideline recommendation used to define the status?

  • Based on these test results, what treatments do you recommend and why?

  • What are the possible side effects of these treatments?

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What Is Metastatic Hormone Receptor

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If you have breast cancer, your medical oncologist and the other members of your care team will use certain key information to help gauge your prognosis and determine the most appropriate treatment. One of these data points is whether the cancer is confined to the breast or has spread to another part of the body. Breast cancer that has moved beyond its point of origin is called metastatic breast cancer.

Another important piece of information is whether the cancer depends on hormones estrogen and/or progesterone to grow. If it does, its known as hormone receptor-positive breast cancer. Around 70% of breast cancers are hormone receptor-positive, according to the American Cancer Society. Metastatic hormone receptor-positive breast cancer is breast cancer that grows with the help of one or both of the female hormones and affects an area of the body beyond the breast.

Currently, metastatic breast cancer, including hormone receptor-positive disease, has no cure. However, modern medicine continues to improve and patients are living longer with each advancement. Cancer specialists use hormone therapy and other treatments to reduce symptoms and help patients enjoy the best quality of life possible.

Progesterone And Breast Cancer

Estrogen alpha receptor antagonists for the treatment of breast cancer ...

Progesterone is another hormone that plays a role in the female reproductive system.

Sometimes breast cancer cells contain progesterone receptors. This is called progesterone receptor positive or PR positive breast cancer, often shortened to PR+.

Invasive breast cancers should also be tested for progesterone receptors.

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How Can Hormones Affect The Growth Of Breast Cancer

Hormones like estrogen and progesterone are chemicals produced by glands in the body. Normally, these hormones help regulate body cycles, like menstruation. However, sometimes these same hormones can cause cancer to grow.

The pathologist will perform tests on the breast cancer cells to determine if they have receptors that feed on estrogen or progesterone, stimulating their growth. If the cancer cells have these receptors, your doctor may recommend hormone therapy drugs, such as blockers or inhibitors. Both types of drugs help to destroy cancer cells by cutting off their supply of hormones.

How To Treat Hormone Sensitive Breast Cancer

Several strategies are used to treat hormone-sensitive breast cancer: Blocking ovarian function: Because the ovaries are the main source of estrogen in premenopausal women, estrogen levels in these women can be reduced by eliminating or suppressing ovarian function. Blocking ovarian function is called ovarian ablation.

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Surgery To Stop The Ovaries From Working

This is also a type of ovarian ablation. You might choose to have an operation to remove your ovaries instead of having drug treatment to stop them working. You have this operation as keyhole surgery. It is called laparoscopic oophorectomy and you have it under general anaesthetic . You usually stay in hospital overnight.

The surgeon makes a number of small cuts into your tummy . They put a long bendy tube called a laparoscope into one of the cuts. The laparoscope connects to a video screen.

The surgeon puts small instruments through the other cuts to carry out the operation and remove the ovaries. They close the cuts with stitches and cover them with small dressings.

Removing your ovaries causes you to have a sudden menopause. The symptoms include hot flushes, sweating and mood swings.

Symptoms Of Metastatic Breast Cancer

Hormone Receptor-Positive Advanced Breast Cancer: Challenges and New Treatment Options

You may know that a lump in the breast is the most common symptom of breast cancer most lumps arent cancerous but its not the only one. Others include breast swelling, breast or nipple pain, red or flaking skin on the breast, abnormal nipple discharge, and swollen lymph nodes under the arms or close to the collarbone.

Lymph node swelling may be a sign that breast cancer is no longer confined to the breast. Metastatic breast cancer can cause a variety of symptoms, including fatigue, nausea, vomiting, poor appetite, and weight loss. Other symptoms of metastatic breast cancer are specific to the site that the disease affects, according to ASCO.

  • If breast cancer spreads to the bones, it can cause pain in the joints, neck, or back. You may also have a higher risk of fractures.
  • Breast cancer that moves to the brain can lead to headaches, nausea, dizziness, and vision problems, among other symptoms.
  • If breast cancer affects the liver, you may experience jaundice yellowing of the skin itchy skin, abdominal swelling, and nausea.
  • Metastatic breast cancer in the lungs can cause respiratory symptoms, such as shortness of breath, difficulty breathing, and a persistent cough.

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Does Estrogen Increase Your Risk Of Breast Cancer

This probably does not increase your risk of developing breast cancer much, if at all. In March 2004, it was concluded from the WHI study that those taking estrogen only had no increased risk of breast cancer or heart disease however, estrogen does appear to increase ones risk of blood clots and stroke.

Can Hormone Therapy Be Used To Prevent Breast Cancer

Yes. Most breast cancers are ER positive, and clinical trials have tested whether hormone therapy can be used to prevent breast cancer in women who are at increased risk of developing the disease.

A large NCI-sponsored randomized clinical trial called the Breast Cancer Prevention Trial found that tamoxifen, taken for 5 years, reduces the risk of developing invasive breast cancer by about 50% in postmenopausal women who were at increased risk . Long-term follow-up of another randomized trial, the International Breast Cancer Intervention Study I, found that 5 years of tamoxifen treatment reduces the incidence of breast cancer for at least 20 years . A subsequent large randomized trial, the Study of Tamoxifen and Raloxifene, which was also sponsored by NCI, found that 5 years of raloxifene reduces breast cancer risk in such women by about 38% .

As a result of these trials, both tamoxifen and raloxifene have been approved by the FDA to reduce the risk of developing breast cancer in women at high risk of the disease. Tamoxifen is approved for this use regardless of menopausal status. Raloxifene is approved for use only in postmenopausal women.

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Hormone Therapy Has A Bigger Impact Than Chemotherapy On Womens Quality Of Life

Cellules cancéreuses. Expression de la protéine PML en rouge et du gène ZNF703 en vert dans des cellules de la lignée de cancer du sein MCF7. ©Inserm/Ginestier, Christophe

Analysis of the CANTO cohort published in the journal Annals of Oncology will upset received wisdom on the effects that hormone therapy and chemotherapy have on the quality of life in women with breast cancer. Contrary to the commonly held view, 2 years after diagnosis, hormone therapy, a highly effective breast cancer treatment worsens quality of life to a greater extent and for a longer time, especially in menopausal patients. The deleterious effects of chemotherapy are more transient. Given that current international guidelines recommend the prescription of hormone therapy for 5 to 10 years, it is important to offer treatment to women who develop severe symptoms due to hormone antagonist medication and to identify those who might benefit from less prolonged or intensive treatment strategies.

This work was directed by Dr Inès Vaz-Luis, specialist breast cancer oncologist and researcher at Gustave Roussy in the lab Predictive Biomarkers and Novel Therapeutic Strategies in Oncology .

Benefits Of Hormone Therapies In Early And Locally Advanced Breast Cancer Treatment

FDA Expands Approval of Fulvestrant for Breast Cancer

Treatment with the hormone therapies tamoxifen and/or an aromatase inhibitor lowers the risk of :

  • Breast cancer recurrence
  • Breast cancer in the opposite breast
  • Death from breast cancer

Premenopausal women who get ovarian suppression plus tamoxifen or an aromatase inhibitor may lower these risks more than premenopausal women who get tamoxifen or an aromatase inhibitor alone .

Learn more about tamoxifen.

Aromatase inhibitor plus androgen deprivation therapy

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