For premenopausal women with primary ER + breast cancer, oophorectomy (OvX) is an evidence-based cost-effective option and is standard treatment in many countries. However, there is virtually no data ...describing the effects of OvX on breast tumour biology. We therefore, characterised the endocrine and genome-wide transcriptional impact of OvX in 56 premenopausal women with ER + breast cancer for 2 weeks prior to mastectomy. Plasma estradiol concentrations decreased from 406 ± 41 to 20.7 ± 2.6 pmol/l (mean ± sem) 24 h after OvX, and to 8.1 ± 0.8 pmol/l 2 weeks later at mastectomy. Ki67 decreased in 33/36 (91.7%) tumours. The expression of 655 genes changed significantly (FDR < 1%) with an absolute mean fold-change (FC) ≥ 1.25 (257 up, 398 down). Archetypal oestrogen-regulated genes (TFF1, GREB1, PGR and PDZK1) showed large decreases in expression (FC = 0.20-0.69;
< 1e-6-1e-7). Proliferation-associated genes (e.g. TOP2A, AURKA and UBE2C) were also strongly downregulated (FC = 0.38-0.56;
< 1e-7) along with putative progesterone-regulated genes (e.g. FKBP4, MYB; FC = 0.64-0.68;
< 1e-4-1e-7). The gene expression changes did not differ according to HER2 status and correlated strongly with the changes reported previously after aromatase inhibitor (AI) treatment in postmenopausal women (rho = 0.55,
< 1e-04). However, after OvX the mean FC was significantly higher compared to AI (
< 1e-04). In conclusion, changes in tumoural gene expression after OvX were largely similar, but of a greater magnitude to those observed after AI in postmenopausal patients; however, OvX appeared to have a greater effect on progesterone-regulated genes than AI.
Breast cancer Mutebi, Miriam; Unger-Saldaña, Karla; Ginsburg, Ophira
Noncommunicable Diseases,
2023, Letnik:
1
Book Chapter
In 2020, an estimated 2.3 million people were diagnosed with breast cancer, making it the commonest cancer among women worldwide. This chapter reviews trends over the past 20 years, key risk factors ...including high body mass index, alcohol use and unhealthy diet, as well as reproductive and family history, particularly BRCA gene variants. In addition to public health interventions to reduce exposure to modifiable risk factors, health systems need to be adequately resourced to ensure that breast cancer is diagnosed and treated early (including through screening programmes whenever feasible) and that quality treatment and care are available for women with breast cancer. The role of oestrogen or progesterone receptors in the diagnosis and treatment of breast cancer is described as are the implications of BRCA mutations when it comes to counselling for women with a family history of breast cancer. Treatment options including surgery, radiation and systemic chemo-, hormone- and targeted immuno- therapy are outlined. The need to ensure that those with advanced cancer have access to palliative care is also emphasized. The importance of networks of care, including with centres of excellence is highlighted, as is ensuring that early diagnosis, treatment and palliative care are included in universal health care benefit packages.
Breast cancer resulted in 700,000 deaths globally in 2019 , with increasing proportions of deaths caused by breast cancer increasing over the last 30 years in all regions, except high-income countries (HICs), partly in line with changes in the age structure of these populations. Ninety-nine percent of breast cancers are in women, with incidence increasing with age. In HICs, most breast cancer cases occur in post-menopausal women, although larger proportions of all cancer deaths are found at younger ages in low- and middle-income countries, when women are pre-menopausal or under age 50, largely reflecting younger populations in these countries. Interventions to reduce exposure to the risk factors common to the four main NCDs are also applicable to breast cancer. Diagnosis of breast cancer requires examination of tissue taken by biopsy and assessment of local and distant spread. Breast cancer is a uniform entity but a spectrum of conditions or subtypes which respond to treatment in different ways.
Byline: Ophira Ginsburg (1), Parviz Ghadirian (2), Jan Lubinski (3), Cezary Cybulski (3), Henry Lynch (4), Susan Neuhausen (5), Charmaine Kim-Sing (6), Mark Robson (7), Susan Domchek (8), Claudine ...Isaacs (9), Jan Klijn (10), Susan Armel (11), William D. Foulkes (12), Nadine Tung (13), Pal Moller (14), Ping Sun (15), Steven A. Narod (15) Keywords: BRCA1; BRCA2; Smoking Among women with a mutation in BRCA1 or BRCA2, the risk of breast cancer is high, but it may be modified by exogenous and endogenous factors. There is concern that exposure to carcinogens in cigarette smoke may increase the risk of cancer in mutation carriers. We conducted a matched case--control study of 2,538 cases of breast cancer among women with a BRCA1 (n = 1,920) or a BRCA2 (n = 618) mutation. One non-affected mutation carrier control was selected for each case, matched on mutation, country of birth, and year of birth. Odds ratios were calculated using conditional logistic regression, adjusted for oral contraceptive use and parity. Ever-smoking was not associated with an increased breast cancer risk among BRCA1 carriers (OR = 1.09 95% CI 0.95--1.24) or among BRCA2 carriers (OR = 0.81 95% CI 0.63--1.05). The result did not differ when cases were restricted to women who completed the questionnaire within two years of diagnosis. A modest, but significant increase in risk was seen among BRCA1 carriers with a past history of smoking (OR = 1.27 95% CI 1.06--1.50), but not among current smokers (OR = 0.95 0.81--1.12). There appears to be no increase in the risk of breast cancer associated with current smoking in BRCA1 or BRCA2 carriers. There is a possibility of an increased risk of breast cancer among BRCA1 carriers associated with past smoking. There may be different effects of carcinogens in BRCA mutation carriers, depending upon the timing of exposure. Author Affiliation: (1) The Campbell Family Institute for Breast Cancer Research at Princess Margaret Hospital, Toronto, ON, Canada (2) Epidemiology Research Unit, Centre Hospitalier de l'Universite de Montreal (CHUM) Hotel-Dieu, Faculty of Medicine, Universite de Montreal, Montreal, QC, Canada (3) Pomeranian Medical University, Szczecin, Poland (4) Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, NE, USA (5) Department of Epidemiology, University of California, Irvine, CA, USA (6) British Columbia Cancer Agency, Vancouver, BC, Canada (7) Clinical Genetics, Department of Medicine, Memorial-Sloan Kettering, New York, NY, USA (8) Departments of Medicine and Genetics, University of Pennsylvania, Philadelphia, PA, USA (9) Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC, USA (10) Department of Medical Oncology, (Dr. Daniel den Hoed Kliniek) Rotterdam Cancer Institute, University Hospital Rotterdam, Rotterdam, The Netherlands (11) Department of Obstetrics and Gynecology, University Health Network, Toronto, ON, Canada (12) Program in Cancer Genetics, Departments of Oncology and Human Genetics, McGill University, Montreal, QC, Canada (13) Beth Israel Deaconess Hospital, Boston, MA, USA (14) Department for Cancer Genetics, The Norwegian Radium Hospital, Oslo, Norway (15) Womens College Research Institute, Women's College Hospital, University of Toronto, 790 Bay Street, 7th Floor, Toronto, ON, Canada, M5G 1N8 (16) Womens College Research Institute, Toronto, ON, Canada Article History: Registration Date: 10/03/2008 Received Date: 19/02/2008 Accepted Date: 10/03/2008 Online Date: 16/05/2008 Article note: Other members of the Hereditary Breast Cancer Clinical Study Group: Olufunmilayo Olopade, Shelly Cummings, Fergus Couch, Barry Rosen, Dominique Stoppa-Lyonnet, Ruth Gershoni-Baruch, David Horsman, Teresa Wagner, Howard Saal, Ellen Warner, Wendy Meschino, Kenneth Offit, Amber Trivedi, Michael Osborne, Dawna Gilchrist, Charis Eng, Jeffrey Weitzel, Wendy McKinnon, Marie Wood, Christine Maugard, Barbari Pasini, Peter Ainsworth, Kevin Sweet, Boris Pasche, Beth Karlan, Raluca N. Kurz, Anna Tulman, Ed Lemire, Jane Mclennan, Gareth Evans, Tomas Byrski, Tomas Huzarski, Jacek Gronwald, Bohdan Gorski, Eitan Friedman, Andrea Eisen, Mary Daly, Judy Garber, Sofia Merajver.
Almost nine of 10 deaths resulting from cervical cancer occur in low-income countries. Visual inspection under acetic acid (VIA) is an evidence-based, cost-effective approach to cervical cancer ...screening (CCS), but challenges to effective implementation include health provider training costs, provider turnover, and skills retention. We hypothesized that a smartphone camera and use of cervical image transfer for real-time mentorship by experts located distantly across a closed user group through a commercially available smartphone application would be both feasible and effective in enhancing VIA skills among CCS providers in Tanzania.
We trained five nonphysician providers in semirural Tanzania to perform VIA enhanced by smartphone cervicography with real-time trainee support from regional experts. Deidentified images were sent through a free smartphone application on the available mobile telephone networks. Our primary outcomes were feasibility of using a smartphone camera to perform smartphone-enhanced VIA and level of agreement in diagnosis between the trainee and expert reviewer over time.
Trainees screened 1,072 eligible women using our methodology. Within 1 month of training, the agreement rate between trainees and expert reviewers was 96.8%. Providers received a response from expert reviewers within 1 to 5 minutes 48.4% of the time, and more than 60% of the time, feedback was provided by regional expert reviewers in less than 10 minutes.
Our method was found to be feasible and effective in increasing health care workers' skills and accuracy. This method holds promise for improved quality of VIA-based CCS programs among health care providers in low-income countries.
The association between sebaceous neoplasms of the skin and visceral cancers, known as Muir-Torre syndrome, is described in three patients, including one with an extensive history of cancer in his ...family. The first patient, a 54-year-old man, developed multiple sebaceous adenomas, epitheliomas, and carcinomas in association with a colonic carcinoma 6 years after cardiac transplantation. Family history in this patient disclosed colon cancer in 17 relatives. The second patient was a 51-year-old man who had recurrent adenocarcinoma of the sigmoid colon, adenocarcinoma arising in Barrett's esophagus, and sebaceous epithelioma during a period of 15 years. The third patient was a 90-year-old man with a sebaceous adenoma followed 5 months later by adenocarcinoma of the sigmoid colon with liver metastases. Muir-Torre syndrome in 129 other patients published in the literature is reviewed. Although it is a rare disease, Muir-Torre syndrome requires recognition because skin lesions may be the first sign of the syndrome and this may lead to early diagnosis of associated visceral cancers. Moreover, because this syndrome appears to be inherited, family members should be screened for visceral cancer, especially colorectal adenocarcinoma.
Breast and colon cancer are among the most common cancers in the developed world. Several epidemiological studies suggest that the occurrence of one of these two cancers in a woman may predispose to ...the development of the other. The occurrence of both forms of cancer in the same woman may be because of chance or common susceptibility. In order to determine how frequently double primary cancers have a hereditary basis, we conducted a registry based study at a single Montreal hospital. Cancer rates in first degree relatives of patients with multiple primaries were compared with provincial age standardised incidence rates and relative risks (RRs) were estimated. In first degree relatives under 45 there was a total of 15 cancers observed, compared with 3.70 expected, giving an RR of 4.05 (95% CI: 2.27-6.68). The RR for colon cancer was significantly increased among male relatives. For relatives less than 45 years old at diagnosis, the RR for colon cancer was 66.7 (95% CI: 13.8-195) (three cases observed, 0.045 expected). For all ages the RR was 5.02 (95% CI: 2.04-10.5). The RR for breast cancer was 5.92 (95% CI: 1.91-13.8) for female relatives under 45 (five cases observed, 0.845 expected) and 2.14 (95% CI: 1.07-3.83) for breast cancer at any age. These results suggest that there may be genes that predispose to both breast and colon cancer in certain people.
Family history and colorectal cancer Narod, S A; Ginsburg, O; Jothy, S
The New England journal of medicine,
1995-Jun-08, Letnik:
332, Številka:
23
Journal Article
We report on a patient with myopathy, kyphoscoliosis, joint contractures, and a facial appearance consistent with King syndrome. Unlike other reported cases, our patient had hyperextensible joints, ...normal stature, and pectus excavatum. The cardiac ventricles, aorta, and pulmonary artery were dilated. Malignant hyperthermia did not occur under anaesthesia although there was a transient increase in CK levels. Muscle bulk and tone were significantly decreased but collagen and elastin fibres were normal. The variable clinical presentation of King syndrome suggests that the manifestations are caused by different congenital myopathies and in all cases there is probably an increased risk of malignant hyperthermia.
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