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Cancer Cell Apr 2020Estrogen receptor-positive (ER) breast cancer is the most common breast cancer subtype. Treatment of ER breast cancer comprises interventions that suppress estrogen... (Review)
Review
Estrogen receptor-positive (ER) breast cancer is the most common breast cancer subtype. Treatment of ER breast cancer comprises interventions that suppress estrogen production and/or target the ER directly (overall labeled as endocrine therapy). While endocrine therapy has considerably reduced recurrence and mortality from breast cancer, de novo and acquired resistance to this treatment remains a major challenge. An increasing number of mechanisms of endocrine resistance have been reported, including somatic alterations, epigenetic changes, and changes in the tumor microenvironment. Here, we review recent advances in delineating mechanisms of resistance to endocrine therapies and potential strategies to overcome such resistance.
Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Disease Management; Drug Resistance, Neoplasm; Female; Humans; Receptors, Estrogen; Tumor Microenvironment
PubMed: 32289273
DOI: 10.1016/j.ccell.2020.03.009 -
American Family Physician Aug 2021Breast cancer is the leading cause of death from cancer in women worldwide, and the second most common cause of death from cancer in women in the United States. Risk... (Review)
Review
Breast cancer is the leading cause of death from cancer in women worldwide, and the second most common cause of death from cancer in women in the United States. Risk assessment tools can identify the risk of breast cancer, and patients at high risk may be candidates for risk-reducing medications. The choice of medication varies with menopausal status. Breast cancer treatment depends on the stage. Stage 0 is ductal carcinoma in situ, which is noninvasive but progresses to invasive cancer in up to 40% of patients. Ductal carcinoma in situ is treated with lumpectomy and radiation or with mastectomy. If ductal carcinoma in situ is estrogen receptor-positive, patients may also receive endocrine therapy. Early invasive stages (I, IIa, IIb) and locally advanced stages (IIIa, IIIb, IIIc) are nonmetastatic and have three treatment phases. The preoperative phase uses systemic endocrine or immunotherapies when tumors express estrogen, progesterone, or ERBB2 receptors. Preoperative chemotherapy may also be used and is the only option when tumors have none of those three receptors. There are two options for the surgical phase with similar survival rates; a lumpectomy with radiation if the tumor can be excised completely with good cosmetic results, or a mastectomy. Sentinel lymph node biopsy is also performed when there is suspected nodal disease. The postoperative phase includes radiation, endocrine therapy, immunotherapy, and chemotherapy. Postmenopausal women should also be offered postoperative bisphosphonates. Stage IV (metastatic) breast cancer is treatable but not curable. Treatment goals include improving the length and quality of life.
Topics: Breast Neoplasms; Combined Modality Therapy; Disease Management; Female; Humans; Neoplasm Staging
PubMed: 34383430
DOI: No ID Found -
Nature Communications Mar 2021The majority of breast cancers express the estrogen receptor (ERα) and agents targeting this pathway represent the main treatment modality. Endocrine therapy has proven... (Review)
Review
The majority of breast cancers express the estrogen receptor (ERα) and agents targeting this pathway represent the main treatment modality. Endocrine therapy has proven successful in the treatment of hormone-responsive breast cancer since its early adoption in the 1940s as an ablative therapy. Unfortunately, therapeutic resistance arises, leading to disease recurrence and relapse. Recent studies increased our understanding in how changes to the chromatin landscape and deregulation of epigenetic factors orchestrate the resistant phenotype. Here, we will discuss how the epigenome is an integral determinant in hormone therapy response and why epigenetic factors are promising targets for overcoming clinical resistance.
Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Drug Resistance, Neoplasm; Epigenesis, Genetic; Epigenomics; Female; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Recurrence, Local; Receptors, Estrogen
PubMed: 33741974
DOI: 10.1038/s41467-021-22024-3 -
Pathologica Apr 2022Phyllodes tumors (PT) are fibroepithelial neoplasms of the breast showing a peculiar leaf-like appearance. They account for 0.3 to 1% of all primary breast tumors and... (Review)
Review
Phyllodes tumors (PT) are fibroepithelial neoplasms of the breast showing a peculiar leaf-like appearance. They account for 0.3 to 1% of all primary breast tumors and 2.5% of all fibroepithelial breast tumors. PT are classified into benign, borderline and malignant based upon their stromal morphology with a distribution of 60%, 20%, and 20%, respectively. Malignant PT of the breast constitute an uncommon challenging group of fibroepithelial neoplasms. They have a relatively high tendency to recur, although distant metastasis is uncommon, and nearly exclusive to malignant PT. Adequate surgical resection remains the standard approach to achieve maximal local control. Giant malignant PT are rare and a pose a diagnostic dilemma for pathologists, especially when comprised of sarcomatous elements. This review highlights the morphological features of PT detected in cytology and histology specimens and discusses diagnostic pitfalls and differential diagnosis.
Topics: Breast; Breast Neoplasms; Female; Humans; Neoplasm Recurrence, Local; Neoplasms, Fibroepithelial; Phyllodes Tumor
PubMed: 35414723
DOI: 10.32074/1591-951X-754 -
The Lancet. Oncology Jan 2022Imaging is paramount for the early detection and clinical staging of breast cancer, as well as to inform management decisions and direct therapy. PET-MRI is a... (Review)
Review
Imaging is paramount for the early detection and clinical staging of breast cancer, as well as to inform management decisions and direct therapy. PET-MRI is a quantitative hybrid imaging technology that combines metabolic and functional PET data with anatomical detail and functional perfusion information from MRI. The clinical applicability of PET-MRI for breast cancer is an active area of research. In this Review, we discuss the rationale and summarise the clinical evidence for the use of PET-MRI in the diagnosis, staging, prognosis, tumour phenotyping, and assessment of treatment response in breast cancer. The continued development and approval of targeted radiopharmaceuticals, together with radiomics and automated analysis tools, will further expand the opportunity for PET-MRI to provide added value for breast cancer imaging and patient care.
Topics: Breast Neoplasms; Female; Humans; Magnetic Resonance Imaging; Multimodal Imaging; Neoplasm Staging; Positron-Emission Tomography; Prognosis
PubMed: 34973230
DOI: 10.1016/S1470-2045(21)00577-5 -
Breast Cancer (Tokyo, Japan) May 2022This systematic review aims to identify the effects of exercise interventions in patients with breast cancer (BCP) and survivors (BCS) on selected variables of physical... (Review)
Review
BACKGROUND
This systematic review aims to identify the effects of exercise interventions in patients with breast cancer (BCP) and survivors (BCS) on selected variables of physical fitness.
METHODS
A comprehensive literature search was conducted using Medline and Scopus. Randomized controlled trials with isolated exercise interventions in BCP and BCS women (< 5 years from therapy completion) were included. The risk of bias (RoB) assessment was conducted using the Cochrane RoB-2-tool. Variables regarding cardiorespiratory fitness (CRF), strength (ST), fatigue (F) and health-related quality of life (HRQoL) were discussed.
RESULTS
Of the 336 studies initially identified, 22 met all the inclusion criteria and were deemed eligible. RoB assessment indicated that the studies had predominantly "some concerns" or had "low RoB", with only 3 studies presenting a "high RoB". The mean duration and frequency of exercise interventions were 19 weeks and 3 sessions/week, performed at moderate intensity (65% VOmax and 66% 1RM, for aerobic and resistance-training interventions, respectively).
CONCLUSIONS
Exercise interventions seem to be a valuable strategy in BCP to avoid the decline of CRF, ST, F and HRQoL. Conversely, improved physical function among BCS is observed for the same variables. Resistance training and combined interventions seem to provide the most encouraging variations of the selected outcomes.
PROSPERO REGISTRATION ID
CRD42021237917.
Topics: Breast Neoplasms; Exercise; Exercise Therapy; Female; Humans; Physical Fitness; Quality of Life; Resistance Training; Survivors
PubMed: 35278203
DOI: 10.1007/s12282-022-01347-z -
Best Practice & Research. Clinical... Jun 2022Although it is uncommon in general, breast cancer is the most commonly diagnosed cancer during pregnancy. While treatment for pregnant patients should adhere to... (Review)
Review
Although it is uncommon in general, breast cancer is the most commonly diagnosed cancer during pregnancy. While treatment for pregnant patients should adhere to treatment guidelines for non-pregnant patients, there exist specific considerations concerning diagnosis, staging, oncological treatment, and obstetrical care. Imaging and staging are preferably performed using breast ultrasound and mammography. Other ionizing radiation imaging modalities, including computed tomography (CT) and Positron Emission Tomography/ Computed Tomography (PET/CT), can be selectively performed when the estimated benefit for the mother outweighs the risks to the foetus, e.g., when the results will change clinical management. MRI is appropriate to stage for distant disease on the indication. Breast cancer during pregnancy is less often hormone receptor-positive and more frequently triple-negative breast cancer compared to age-matched controls. The basic principle is that women should receive state-of-the-art oncological treatment without delay if possible and that the pregnancy should be maintained as long as possible. Treatment strategy should be multidisciplinary defined, carefully weighing the selection, sequence, and timing of treatment modalities depending on patient-, tumour-, and pregnancy-related characteristics, as well as patient preferences. Initiating cancer treatment during pregnancy often decreases the risks of early delivery and prematurity. Breast cancer surgery is possible during all trimesters. Radiotherapy is possible during pregnancy in the first half of pregnancy. Chemotherapy can be safely administered starting from 12 weeks of gestational age, but endocrine and HER2 targeted therapy are contraindicated throughout the whole pregnancy. Importantly, foetal growth should be monitored and long-term follow-up of the children is encouraged in dedicated centres.
Topics: Breast; Breast Neoplasms; Female; Humans; Mammography; Neoplasm Staging; Phenotype; Positron Emission Tomography Computed Tomography; Pregnancy
PubMed: 35644793
DOI: 10.1016/j.bpobgyn.2022.05.001 -
British Journal of Cancer Feb 2022Breast cancer accounts for 25% of the cancers in women worldwide. The most common subtype of breast cancer diagnosed is hormone receptor positive, which expresses the... (Review)
Review
Breast cancer accounts for 25% of the cancers in women worldwide. The most common subtype of breast cancer diagnosed is hormone receptor positive, which expresses the oestrogen receptor (ER). Targeting of the ER with endocrine therapy (ET) is the current standard of care for ER-positive (ER+) breast cancer, reducing the mortality by up to 40%. Resistance to ET, however, remains a major issue for ER + breast cancer, leading to recurrence and metastasis. One major driver of ET resistance is mutations in the ER gene (ESR1) leading to constitutive transcriptional activity and reduced ET sensitivity. These mutations are particularly detrimental in metastatic breast cancer (MBC) as they are present in as high as 36% of the patients. This review summarises the pre-clinical characterisation of ESR1 mutations and their association with clinical outcomes in MBC and primary disease. The clinically approved and investigational therapeutic options for ESR1 mutant breast cancer and the current clinical trials evaluating ESR1 mutations and ET resistance are also discussed. Finally, this review addresses pre-clinical models and multi-'omics' approaches for developing the next generation of therapeutics for ESR1 mutant and ET-resistant breast cancer.
Topics: Breast Neoplasms; Drug Resistance, Neoplasm; Estrogen Receptor alpha; Female; Humans; Molecular Targeted Therapy; Mutation; Neoplasm Metastasis
PubMed: 34621045
DOI: 10.1038/s41416-021-01564-x -
Nature Reviews. Cancer Oct 2023The hormone receptor oestrogen receptor-α (ER) orchestrates physiological mammary gland development, breast carcinogenesis and the progression of breast tumours into... (Review)
Review
The hormone receptor oestrogen receptor-α (ER) orchestrates physiological mammary gland development, breast carcinogenesis and the progression of breast tumours into lethal, treatment-refractory systemic disease. Selective antagonism of ER signalling has been one of the most successful therapeutic approaches in oncology, benefiting patients as both a cancer preventative measure and a cancer treatment strategy. However, resistance to anti-oestrogen therapy is a major clinical challenge. Over the past decade, we have gained an understanding of how breast cancers evolve under the pressure of anti-oestrogen therapy. This is best depicted by the case of oestrogen-independent mutations in the gene encoding ER (ESR1), which are virtually absent in primary breast cancer but highly prevalent (20-40%) in anti-oestrogen-treated metastatic disease. These and other findings highlight the 'evolvability' of ER breast cancer and the need to understand molecular processes by which this evolution occurs. Recent development and approval of next-generation ER antagonists to target ESR1-mutant breast cancer underscores the clinical importance of this evolvability and sets a new paradigm for the treatment of ER breast cancers.
Topics: Humans; Female; Breast Neoplasms; Drug Resistance, Neoplasm; Estrogens; Signal Transduction
PubMed: 37500767
DOI: 10.1038/s41568-023-00604-3 -
Pathologica Mar 2020The World Health Organization's new classification of breast tumors has just been published. This review aims to examine the morphological categorization of breast... (Review)
Review
The World Health Organization's new classification of breast tumors has just been published. This review aims to examine the morphological categorization of breast carcinomas which is still principally based on histological features and follows the traditions of histological typing. It gives a subjective and critical view on the WHO classifications and their changes over time, and describes the changes related to some of the most common or challenging breast carcinomas: in situ carcinomas, invasive breast carcinomas of no special type, lobular, cribriform, tubular, mucinous, papillary, metaplastic carcinomas and carcinomas with medullary pattern and those with apocrine differentiation are discussed in more details. Although the 5 edition of the classification is not perfect, it has advantages which are mentioned along with problematic issues of classifications.
Topics: Breast Neoplasms; Humans; Neoplasm Grading; Time Factors; World Health Organization
PubMed: 32202537
DOI: 10.32074/1591-951X-1-20