Which Patients Benefit From The Inclusion Of Ovarian Function Suppression As Part Of The Adjuvant Endocrine Therapy Regimen
Given the added toxicity and relatively modest benefit in distant DFS,7,21 subset analyses are being used to determine which patients benefit most from the addition of ovarian function suppression to endocrine therapy. In the SOFT trial,7,21 patients who received chemotherapy were noted to have improved DFS with ovarian function suppression with either tamoxifen or exemestane compared with tamoxifen alone. This difference was especially notable in the small number of patients younger than 35 years of age, where the rate of freedom from breast cancer differed markedly for tamoxifen alone versus tamoxifen plus ovarian function suppression versus exemestane plus ovarian function suppression .
Moreover, in the planned subset analysis of SOFT/TEXT trials for patients receiving adjuvant chemotherapy, there was evidence of benefit for tamoxifen plus ovarian function suppression versus tamoxifen alone in terms of reduction of breast cancer recurrences at 5 years , with a further improvement among those receiving exemestane plus ovarian function suppression .21 However, the receipt of chemotherapy among patients was high , especially among younger women.
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It Will Also Be Important In The Future To Differentiate Prior To Treatment Patients Who Are At High Risk Of Relapse From Those At Lower Risk In Order To Tailor Hormone Treatment This May Be Done To Avoid Escalation Of Anti
The CANTO cohort comprises 12,000 women with breast cancer treated in 26 French centres. It is sponsored by Unicancer and directed by Professor Fabrice André, specialist breast cancer oncologist at Gustave Roussy, Inserm research director and responsible of the lab Predictive Biomarkers and Novel Therapeutic Strategies in Oncology . Its objective is to describe adverse effects associated with treatment, to identify the populations at risk of developing them and to adjust therapy accordingly, so as to afford a better quality of life following cancer.
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J Clin Oncol. 2019 Feb 10 37:423-438 : https://doi.org/10.1200/JCO.18.01160
TO CITE THIS POST :
1INSERM Unit 981, Gustave Roussy, Cancer Campus, Villejuif, France
2Breast Unit, Champalimaud Clinical Center, Champalimaud Foundation, Lisbon, Portugal
3Medical Oncology, Gustave Roussy, Cancer Campus, Villejuif
4Department of Supportive Care, Gustave Roussy, Cancer Campus, Villejuif
5Medical Oncology, Centre François Baclesse Caen, Caen
6Unicancer, Paris, France
7Department of Medical Oncology, U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova
8Department of Internal Medicine and Medical Specialties , School of Medicine, University of Genova, Genova, Italy
9Surgical Oncology, Centre Georges-François Leclerc, Dijon
10Medical Oncology, Institut Curie, Paris
14Surgical Oncology, C.R.L.C Val dAurelle, Montpellier
Postmenopausal Hormone Use Linked With Specific Types Of Breast Cancer
According to the results of a study published in the journal Lancet Oncology, use of postmenopausal hormones increases the risk of lobular and tubular breast cancers more than other types of breast cancer.13
A question that has remained uncertain is whether the link between postmenopausal hormones and breast cancer varies by type of breast cancer. To explore this question, researchers evaluated information from the U.K. Million Women Study.9 The study enrolled over one million women between the ages of 50 and 64.
During follow-up, roughly 14,000 of the women were diagnosed with breast cancer. Close to 12,000 of these diagnoses were invasive breast cancer and the remainder was in situ breast cancer .
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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:
Will The Nhs Fund An Unlicensed Medicine
Its possible for your doctor to prescribe a medicine outside the uses its licensed for if theyre willing to take personal responsibility for this off-licence use of treatment.
Your local integrated care board may need to be involved, as it would have to decide whether to support your doctors decision and pay for the medicine from NHS budgets.
Page last reviewed: 28 October 2019 Next review due: 28 October 2022
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Overall Survival According To History Of Mht Use
During follow-up, a total of 111 patients died of which 59 patients had a previous recurrence. There were 51 deaths in ever MHT users and 60 deaths among never users. KaplanMeier analysis showed a significant association between ever MHT use and a longer OS vs. patients who never used MHT . The crude HR for ever MHT use was 0.68 compared with never use. However, when adjusted for covariates, the statistical analysis showed no significant difference in survival between ever MHT users and never MHT users, HRadj 0.81 . There were significant effect modifications between ever MHT use and OS depending on axillary lymph node involvement and AI treatment but not with other patient, tumor, or treatment related factors.
Ever MHT use was associated with lower risk of death in node-positive patients with a HRadj of 0.48 but not in node-negative patients, HRadj of 1.27 . Moreover, any MHT use was associated with a lower risk of death in AI-treated patients with a HRadj of 0.41 , but not in non-AI-treated patients HRadj of 1.23 , adjusted Pinteraction = 0.015), see Table 2 and Figure 4.
Pros And Cons Of Hormone Therapy For Breast Cancer
Hormone therapy for breast cancer is a good option for breast cancers that are sensitive to hormones. Most common types of hormone therapy for breast cancer work by obstructing hormones from getting attached to receptors on cancer cells or by lowering the making of hormones in the body. Although a trustable treatment for breast cancers that have receptors for the naturally happening hormones estrogen or progesterone it is good to have an overview of hormone therapy for breast cancer pros and cons.
It is commonly used following surgery to lower the risks of cancer recurrence. This treatment can even be used to lessen a tumor before surgery. Once the breast cancer diagnosis traces it is due to hormones this treatment should be the best option.
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If Cancer Comes Back Or Has Spread
AIs, tamoxifen, and fulvestrant can be used to treat more advanced hormone-positive breast cancers, especially in post-menopausal women. They are often continued for as long as they are helpful. Pre-menopausal women might be offered tamoxifen alone or an AI in combination with an LHRH agonist for advanced disease.
Personalized Insights For Personalized Treatment
Just as every patient is different, so is every tumor. The Breast Recurrence Score test uses genomics to give you and your doctor important risk information about how your individual tumor will likely behave. Valuable insights include:
- How likely you are to benefit from chemotherapy
- How likely your tumor is to spread
- The risk of your cancer recurring
- How likely your tumor is to respond to hormone therapy alone
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How To Choose The Best Kind Of Hormone Therapy
There are many hormone therapy types to cure breast cancer such as
Selective Estrogen Receptor Modulators
Even known as SERMs, these medications obstruct breast cancer cells from getting attached to estrogen. SERMs impede the effects of estrogen merely in breast tissue but not in other tissues within the body.
These drugs are traditionally only used in premenopausal women.
The commonly used SERMs consist
Tamoxifen
This medication stops estrogen from attaching to cells and thereby disables cancer from growing and dividing. People who have tamoxifen for a decade after breast cancer treatment are less supposed to see the cancer recurrence and more supposed to live longer in comparison to the ones who take the medicine for just 5 years.
Toremifene
This medication is approved only to cure breast cancer that has extended to other body parts and might not be useful in persons who have seen less success with tamoxifen.
Fulvestrant
This is an injected estrogen receptor-blocking medication that is usually used to cure advanced breast cancers. Different from other SERMs, it obstructs the effect of estrogen all through the total body.
Aromatase Inhibitors
AIs obstruct estrogen production from fat tissue, however, have no consequence on the estrogen made by the ovaries.
Common AIs consist
Ovarian Ablation or Suppression
Surgical ablation is carried on by the removal of ovaries. Without the manufacturing of estrogen from the ovaries, one will move into permanent menopause.
Premenopausal Women Responded Better To Hormone Therapy And Chemotherapy
Of the women enrolled in the RxPonder trial, 3,350 were postmenopausal and 1,665 were premenopausal. Further analysis by menopausal status revealed that there was no difference in five-year survival for postmenopausal women treated with hormone therapy alone versus hormone therapy with chemotherapy.
However, for premenopausal women there was a 46% reduction in the risk of invasive disease. For this subgroup of women, the five-year, invasive disease-free survival rates were 94.2% in women treated with hormone therapy and chemotherapy, compared to 89% in women treated with hormone therapy alone. The premenopausal women who received both chemotherapy and hormone therapy had an additional benefit of around 5%. It is unclear if the survival benefit seen in premenopausal women is primarily due to chemotherapys effect, or indirectly by ovarian suppression due to chemotherapy
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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:
How Is Hormone Therapy Used To Treat Breast Cancer
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.
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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 .
What Does This Mean For Breast Cancer Treatment Decision
The treatment of breast cancer has truly become personalized. It has always been important to know the stage of your caner, but now it is also important to know the type of your cancer. With this information, women can make an informed discussion with their oncologist about the risks and benefits of chemotherapy.
If you are a premenopausal woman with a HR-positive, node-positive breast cancer, chemotherapy and hormone therapy may give you the greatest chance of decreasing your risk of the cancer coming back. However, for a postmenopausal woman with HR-positive breast cancer, chemotherapy may not add many treatment benefits to hormone therapy, and it carries risks that may affect your quality of life. Studies like the TailorRx and RxPonder trials have provided more information to help you make an informed decision.
About the Author
T. Salewa Oseni, MD, Contributor
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Stopping The Ovaries Working
In premenopausal women, doctors might use a type of hormone treatment to stop the ovaries from producing oestrogen. This type of drug is called a luteinising hormone releasing hormone . For example, goserelin and leuprorelin . You might have this on its own or with other hormone therapy drugs.
LHRH drugs work by blocking a hormone made in the pituitary gland that stimulates your ovaries to make and release oestrogen. This stops your ovaries from working. So you won’t have periods or release eggs while you are having the injections.
When you stop taking the drug, your ovaries should start working again. But, if you’re close to the age at which your menopause would naturally start, your periods might not start again.
Menopausal Status And Chemotherapy
Menopause has been broadly defined as age > 60, having undergone bilateral oophorectomy , or having amenorrhea for at least 12 months in the absence of factors potentially influencing menstruation 13. Confirming menopausal status can pose a challenge in women either who have undergone hysterectomy without BSO or who develop chemotherapy-induced ovarian failure . Women under age 60 with HR+ breast cancer who have undergone hysterectomy without BSO and who will be receiving chemotherapy should have ovarian function assessed prior to chemotherapy initiation in order to determine pre-chemotherapy menopausal status. This information helps inform choice of endocrine therapy and potential need for monitoring of ovarian function.
Women with CIOF can experience reactivation of ovarian function during AI therapy despite having estradiol concentrations in the postmenopausal range at the time of AI initiation14,15. Importantly, estradiol levels can increase even though menses do not resume. Notably, younger age at the time of chemotherapy is independently associated with a higher chance of ovarian function recovery following AI therapy, and no upper age limit has yet been identified15.
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If Cancer Has Come Back Or Spread
Hormone therapy can be used to treat breast cancer that has come back or that has spread to another part of the body .
Its given either alone or with other treatments, depending on what treatments you had before.
If your breast cancer came back during or after treatment with hormone therapy, you may be offered a different type of hormone therapy.
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