Women who inherit a deleterious
or
mutation face substantially increased risks of developing breast cancer, which is estimated at 70%. Although annual screening with magnetic resonance imaging (MRI) ...and mammography promotes the earlier detection of the disease, the gold standard for the primary prevention of breast cancer remains bilateral mastectomy. In the current paper, I review the evidence regarding the management of healthy
mutation carriers, including key risk factors and protective factors, and also discuss potential chemoprevention options. I also provide an overview of the key findings from the literature published to date, with a focus on data from studies that are well-powered, and preferably prospective in nature.
Arsenic is a widespread environmental contaminant and recognized carcinogen for the skin, bladder and lungs. In recent years, there has been an increasing number of studies that have investigated the ...effects of arsenic exposure and cancer risk at other sites, including the breast. However, to date, the association between arsenic exposure and breast cancer risk remains unclear. This article will provide an overview of arsenic metabolism, the clinically important biomarkers commonly used to assess arsenic exposure, and review the epidemiologic studies examining the role of arsenic exposure on breast cancer risk. Given the large burden of disease associated with breast cancer, it is of the upmost importance to identify risk factors and preventative strategies that could reduce cancer incidence. Limiting exposure to endemic environmental toxins, such as arsenic, represents one such strategy. More studies are required to better ascertain this relationship and to develop the public policy necessary to significantly reduce breast cancer incidence.
BRCA1 and BRCA2 mutation carriers face an elevated lifetime risk of developing ovarian cancer. Oral contraceptives have been shown to significantly decrease the risk of ovarian cancer by ...approximately 50% in this high-risk population. Changes in contraceptive formulations and patterns of use over time have introduced lower hormonal dosages, different steroid types and non-oral routes of administration. Specifically, there has been a considerable shift in patterns of contraceptive use and the increase in the uptake of non-oral, long-acting, reversible contraception (e.g., intrauterine devices, implants, injections) has corresponded to a decline in oral contraceptive pill use. Whether or not these other methods confer a protective effect against ovarian cancer in the general population is not clear. To our knowledge, there have been no such studies conducted among BRCA mutation carriers. Furthermore, the impact of these changes on the risk of developing ovarian cancer is not known. In this article, we will review the existing epidemiologic evidence regarding the role of contraceptives and the risk of ovarian cancer with a focus on women with a BRCA1 or BRCA2 mutation. We will discuss recent findings and gaps in the knowledge while extrapolating from studies conducted among women from the noncarrier population.
Prescribing fell after the publicity stemming from the Women's Health Initiative (WHI) trial reports in 20021 and 2004,2 which showed an increase in the risk of breast cancer with the use of ...combination therapy (oestrogen and progesterone). The decline in menopausal hormone therapy (MHT) use was followed by a decline in the incidence of breast cancer3 (fear of breast cancer likely had the greatest effect on the use of hormone replacement therapy HRT, but to my knowledge this has not been formally established).3 Perhaps breast cancer worry has deprived millions of women of an effective remedy for some of the symptoms of menopause. Clinicians must heed the message of this study but also to take a rational and comprehensive approach to the management of menopausal symptoms, with careful consideration of the risks and benefits of initiating MHT for each woman.6 This might be dependent on severity of the symptoms, contraindications for MHT (ie, breast cancer, cardiovascular disease, and stroke), and BMI, and could take into account patient preference.6 For likely candidates, MHT (preferably oestrogen alone) should be initiated around the time of natural menopause and ideally limited to 5 years of use.
Women with a pathogenic germline mutation in the BRCA1 gene face a very high lifetime risk of developing breast cancer, estimated at 72% by age 80. Prophylactic bilateral mastectomy is the only ...effective way to lower their risk; however, most women with a mutation opt for intensive screening with annual MRI and mammography. Given that the BRCA1 gene was identified over 20 years ago, there is a need to identify a novel non-surgical approach to hereditary breast cancer prevention. Here, we provide a review of the emerging preclinical and epidemiologic evidence implicating the dysregulation of progesterone-mediated receptor activator of nuclear factor κB (RANK) signaling in the pathogenesis of BRCA1-associated breast cancer. Experimental studies have demonstrated that RANK inhibition suppresses Brca1-mammary tumorigenesis, suggesting a potential target for prevention. Data from studies conducted among women with a BRCA1 mutation further support this pathway in BRCA1-associated breast cancer development. Progesterone-containing (but not estrogen-alone) hormone replacement therapy is associated with an increased risk of breast cancer in women with a BRCA1 mutation. Furthermore, BRCA1 mutation carriers have significantly lower levels of circulating osteoprotegerin (OPG), the decoy receptor for RANK-ligand (RANKL) and thus endogenous inhibitor of RANK signaling. OPG levels may be associated with the risk of disease, suggesting a role of this protein as a potential biomarker of breast cancer risk. This may improve upon current risk prediction models, stratifying women at the highest risk of developing the disease, and further identify those who may be targets for anti-RANKL chemoprevention. Collectively, the evidence supports therapeutic inhibition of the RANK pathway for the primary prevention of BRCA1-associated breast cancer, which may generate unique prevention strategies (without prophylactic surgery) and enhance quality of life.
Ovarian cancer has a high case fatality rate, but patients who have no visible residual disease after surgery have a relatively good prognosis. The presence of any cancer cells left in the peritoneal ...cavity after treatment may precipitate a cancer recurrence. In many cases, these cells are occult and are not visible to the surgeon. Analysis of circulating tumour DNA in the blood (ctDNA) may offer a sensitive method to predict the presence of occult (non-visible) residual disease after surgery and may help predict disease recurrence. We assessed 48 women diagnosed with serous ovarian cancer (47 high-grade and 1 low-grade) for visible residual disease and for ctDNA. Plasma, formalin-fixed paraffin-embedded (FFPE) tumour tissue and white blood cells were used to extract circulating free DNA (cfDNA), tumour DNA and germline DNA, respectively. We sequenced DNA samples for 59 breast and ovarian cancer driver genes. The plasma sample was collected after surgery and before initiating chemotherapy. We compared survival in women with no residual disease, with and without a positive plasma ctDNA test. We found tumour-specific variants (TSVs) in cancer cells from 47 patients, and these variants were sought in ctDNA in their post-surgery plasma. Fifteen (31.9%) of the 47 patients had visible residual disease; of these, all 15 had detectable ctDNA. Thirty-one patients (65.9%) had no visible residual disease; of these, 24 (77.4%) patients had detectable ctDNA. Of the patients with no visible residual disease, those patients with detectable ctDNA had higher mortality (20 of 27 died) than those without detectable ctDNA (3 of 7 died) (HR 2.32; 95% CI: 0.67–8.05), although this difference was not statistically significant (p = 0.18). ctDNA in post-surgical serum samples may predict the presence of microscopic residual disease and may be a predictor of recurrence among women with ovarian cancer. Larger studies are necessary to validate these findings.
Platelet Count and Survival after Cancer Giannakeas, Vasily; Kotsopoulos, Joanne; Brooks, Jennifer D ...
Cancers,
01/2022, Letnik:
14, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Thrombocytosis is associated with cancer progression and death for many cancer types. It is unclear if platelet count is also associated with cancer survival. We conducted a cohort study of 112,231 ...adults in Ontario with a diagnosis of cancer between January 2007 and December 2016. We included patients who had a complete blood count (CBC) completed in the 30 days prior to their cancer diagnosis. Subjects were assigned to one of three categories according to platelet count: low (≤25th percentile), medium (>25 to <75th percentile), and high (≥75th percentile). Study subjects were followed from the date of their cancer diagnosis for cancer-specific death. Of the 112,231 eligible cancer patients in the cohort study, 40,329 (35.9%) died from their cancer in the follow-up period. Relative to those with a medium platelet count, the rate of cancer-specific death was higher among individuals with a high platelet count (HR 1.52; 95%CI 1.48-1.55) and was lower among individuals with a low platelet count (HR 0.91; 95%CI 0.88-0.93). A high platelet count was associated with poor survival for many cancer types. Platelet count could potentially be used as a risk stratification measure for cancer patients.
Observational studies have reported an inverse relationship between selenium status (blood or toenail) and the risk of laryngeal cancer; however, the impact of low serum selenium level on survival ...has not been evaluated.
We conducted a prospective study of 296 patients diagnosed with laryngeal cancer in Szczecin, Poland. Serum selenium was measured at diagnosis and prior to treatment. Patients were followed from the date of diagnosis to death at five years. Vital status was obtained by linkage to the Polish National Death Registry.
The five-year survival after diagnosis was 82.0% (95% CI: 68% to 91%) for individuals in the highest quartile of serum selenium (> 66.8 μg/L) and was 28.6% (95% CI 19% to 42%) for individuals in the lowest quartile (<50.0 μg/L). In an age- and sex-adjusted analysis, the hazard ratio (HR) for death from all causes was 7.01 (95% CI 3.81 to 12.9) for patients in the lowest quartile of serum selenium, compared to those in the highest quartile. The corresponding multivariate HR was 3.07 (95% CI 1.59 to 5.94).
This study suggests that a selenium level in excess of 70 μg/L is associated with improved outcome among patients undergoing treatment for laryngeal cancer. Further studies are needed to evaluate if selenium supplementation to achieve this level might improve overall prognosis.
Abstract Objective Preventive breast surgery and MRI screening are offered to unaffected BRCA mutation carriers. The clinical benefit of these two modalities has not been evaluated among mutation ...carriers with a history of ovarian cancer. Thus, we sought to determine whether or not BRCA mutation carriers with ovarian cancer would benefit from preventive mastectomy or from MRI screening. Methods First, the annual mortality rate for ovarian cancer patients was estimated for a cohort of 178 BRCA mutation carriers from Ontario, Canada. Next, the actuarial risk of developing breast cancer was estimated using an international registry of 509 BRCA mutation carriers with ovarian cancer. A series of simulations was conducted to evaluate the reduction in the probability of death (from all causes) associated with mastectomy and with MRI-based breast surveillance. Cox proportional hazards models were used to evaluate the impacts of mastectomy and MRI screening on breast cancer incidence as well as on all-cause mortality. Results Twenty (3.9%) of the 509 patients developed breast cancer within ten years following ovarian cancer diagnosis. The actuarial risk of developing breast cancer at ten years post-diagnosis, conditional on survival from ovarian cancer and other causes of mortality was 7.8%. Based on our simulation results, among all BRCA mutation-carrying patients diagnosed with stage III/IV ovarian cancer at age 50, the chance of dying before age 80 was reduced by less than 1% with MRI and by less than 2% with mastectomy. Greater improvements in survival with MRI or mastectomy were observed for women who had already survived 10 years after ovarian cancer, and for women with stage I or II ovarian cancer. Conclusions Among BRCA mutation-carrying ovarian cancer patients without a personal history of breast cancer, neither preventive mastectomy nor MRI screening is warranted, except for those who have survived ovarian cancer without recurrence for ten years and for those with early stage ovarian cancer.
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