Cancer on hormonal therapy, Cancer on hormonal therapy
It is applied in patients expressing tumoral hormone receptors ER - estrogen receptor and PGR - progesteron receptor. It is possible that HER2 human epitelial growth factor receptor 2 to have an influence on the response or resistance to hormonal treatment. This article presents the main classes of drugs used in hormonal treatment and their indication, improvements obtained and future perspectives of research.
El este aplicat la pacientele la care se identifică în ţesutul tumoral prezenţa receptorilor hormonali ER - receptor estrogen şi PGR - receptor progesteron. Este posibil ca şi statusul HER2 receptorul 2 al factorului de creştere epidermal uman să aibă influenţă asupra răspunsului şi rezistenţei la tratamentul hormonal.
Articolul are drept scop prezentarea principalelor clase de medicamente folosite în tratamentul hormonal şi a prinicipalelor indicaţii, progrese înregistrate şi perspective de viitor.
Actualizări în tratamentul hormonal al cancerului de sân
Cuvinte cheie tratament hormonal cancer de sân modulatori selectivi ai receptorului de estrogen inhibitori de aromatază Introduction Hormones are molecules that act like chemical messengers in the human cancer on hormonal therapy.
Their main circulating path is through the blood stream. Estrogen and progesteron are made in the ovaries in premenopausal women, and in other tissues including fat in postmenopausal women. Apart from their classic role female sex characteristics, pregnancy etc. To determine the hormonal status, tissue from the tumour is needed.
It can be obtained either by biopsy, or by surgery. Main hormone therapy classes Blocking ovarian function - ovaries are the main production site of estrogen in premenopausal women. Blocking of their function can be achieved by either removing ovaries surgically, or by radiation both being definitive methods or, most frequently used today, inhibiting their function temporarily by using gonadotropin releasing hormone GnRH agonists or luteinizing hormone releasing hormone LH-RH agonists.
Cancer on hormonal therapy. Romania Cancer Oranisations and Resources | CancerIndex
Examples: goserelin and leuprolide. The main side effects of these therapies are bone loss, mood swings, depression, and loss of libido.
Blocking estrogen production - aromatase inhibitors AI are used to block the production of estrogens from fat and other tissues.
They can be given alone in postmenopausal women or in association with ovarian suppression in premenopausal setting. Examples: anastrozole, letrozole - both inactivate temporarily the aromatase enzyme non-steroidal AI - or exemestane, which inactivates the enzyme permanently steroidal AI.
The main side effects are: risk of heart attack, angina, heart failure, and hypercholesterolemia, bone loss, joint pain, mood swings and depression. Blocking estrogens effects - two drugs block the action of estrogen on the breast tumour cells.
Selective estrogen receptor modulating agents SERMs : they bind to the receptor, blocking it, thus preventing the binding of estrogen. Examples: tamoxifen and toremifen. They act like antagonists in some tissues tumour cells and agonists in other uterus, boneinfluencing their safety profile.
Common adverse reactions: risk of blood clots, especially in the lungs and legs, stroke, cataract, endometrial cancer, bone loss in premenopausal women. Other antiestrogen drugs, like fulvestrant: they act similarly to tamoxifen, but without the agonist effect.
Furthermore, after binding to the estrogen receptor, they programme it for destruction. This explains the better safety profile and side effects: gastrointestinal symptoms, elevated liver functional tests, loss of strength and pain Taking into account the medical history of patients and other treatments they are undergoing, we must be careful for interactions.
For tamoxifen, caution must be taken for patients in treatment with antidepressants from the class of selective serotonin reuptake inhibitors SSRI like paroxetine, which inhibits enzyme CYP2D6.
They slow down tamoxifen metabolization and reduce its effects. Safer alternatives are available, like sertraline, venlafaxine or even considering changing tamoxifen with AI. Treatment protocols Prevention. The same indication for AI is still under investigation 8.
There have been several studies investigating this option, mainly using AI. The purpose is to obtain tumour shrinkage in order cancer on hormonal therapy allow breast conserving surgery. Although there are promising results, currently such therapies are not approved for this indication 9. Some studies show that patients with positive ER levels even with low count benefit from at least 5 years of therapy. Newer studies extend this period to 7 or even 10 years.
In premenopausal patients at high risk young age, high grade tumour, lymph node involvmentaromatase inhibitor with associated ovarian suppression or tamoxifen for 5 years can be considered based on SOFT and TEXT trials results.
Cancer hormonal therapy side effects.
There are different strategies, involving either starting with tamoxifen for years, then switching to AI or tamoxifen for 5 years and switching afterwards, or starting with AI plus ovarian suppression. Also, we must bear in mind the adverse reactions profile. For tamoxifen, the cardiovascular risk and of uterine cancer requiring anual echographic monitoringand for AI, mainly the risk for bone health annual DEXA and supplements of calcium, vitamin D and even agents like zoledronic acid or denosumab Endocrine therapy is fairly well supported, with tolerable side effects, cancer on hormonal therapy should be given in patients with non-visceral or asymptomatic, and with not high-volume visceral tumours, especially in patients with suggestive factors for good response indolent disease, old age, long disease free interval.
There is also the option of fulvestrant, after progression after antiestrogen therapy. There is a benefit to switch non-steroidal AI like anastrozole with steroidal AI like exemestane after disease progression, if not facing visceral crisis The results of PALOMA-2 trial published in November showed a significant longer progression-free survival in patients on palociclib in combination with letrozole compared to patients on letrozole alone.
However, the addition of palciclib caused higher rates of myelotoxic events in the study along with fatigue, nausea, mouth sores, hair loss, and diarrhea. For patients who already progressed on an AI, palbociclib can be given along with fulvestrant Resistance to hormonal treatment Despite good tolerance and response obtained, primary and secondary resistance to hormonal treatment is a concerning reality; phase III studies show that in metastatic breast cancer with positive hormone receptors, only one third of patients have radiological response after IA.
And even in the patients who initially respond, at some point they all develop resistance to cancer on hormonal therapy, progression, and finally death 18, There are several hypotheses for acquired hormonal resistance: altered expression of ER coregulators, downregulation of ER expression, ER mutations and ligand-independent activation of ER - probably, in real life situations experiencing a combination of all above.
It is well known that tumours exhibiting HER2 human epidermal growth factor receptor 2 are more aggressive and have the worst prognostic. There is evidence suggesting that HER family like HERand especially overexpression of HER 2, cancer on hormonal therapy intrinsec resistance to hormonal treatment, thus sustaining the rationale of using also targeted treatment for this case Also, there seems to be a place for liquid biopsies in monitoring response to hormonal treatment and prognosis worse for patients identified with ER mutations by this method Further studies are needed for identifing and characterizing mechanisms of resistance and methods to overcome them.
Conclusions In treating breast cancer, every treatment has its use and rationale. It is obvious that a hormonal treatment with low adverse reaction is preferred for most of the patients, even in the presence of visceral metastasis asymptomatic.
The further development of molecular profiling some already available in certain areas - MammaPrint, Oncotype Dxbiomarkers and techniques involving circulating tumour cells seem to bring us closer to the ideal of personalized medicine, where patients receive the treatment that yields the best results for them. Bibliografie 1. Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients.
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Journal of the National Cancer Institute ; 17 — Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. JAMA Neoadjuvant endocrine therapy in primary breast cancer: indications and use as a research tool.
British Journal of Cancer ; 6 — Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials.
Cancer on hormonal therapy
Lancet ; — Untch M, Thomssen C. Clinical practice decisions in endocrine therapy. Cancer Investigation ; 28 Suppl — Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1—98 randomised clinical trial at 8.
Lancet Oncology ; 12 12 — Adjuvant hormonal therapy for early-stage breast cancer. Surgical Oncology Clinics of North America ; 19 3 — Prudence A. Francis MD. Bertelli G. Sequential treatment with exemestane and non-steroidal aromatase inhibitors in advanced breast cancer. Epub Jan J Clin Oncol 34, suppl; abstr Abstract LBA1.
Actualizări în tratamentul hormonal al cancerului de sân
Bonneterre J et al. J Clin Oncol — Nabholtz JM et al. Ali S et al. Nat Rev Cancer 2: — Yarden Y et al. Nat Rev Mol Cell Biol 2: — Nat Rev Cancer 5: — Memorial Sloan Kettering Cancer Center. Potential of liquid biopsy for breast cancer patients: Simple blood test could help tailor treatments for advanced breast cancer patients. ScienceDaily, 11 Decemberwww. Experienţa unui centru din România Silvia Moşoiu, Conf. Laurenţia Galeş, Denisa Ciochir Cancerul de sân este cel mai frecvent tip de cancer diagnosticat la femeile din întreaga lume şi principala cauză de mortalitate printre acestea.