Purpose
Changes occur in the expression of oestrogen-regulated and proliferation-associated genes in oestrogen receptor (ER)-positive breast tumours during the menstrual cycle. We investigated if ...Oncotype® DX recurrence score (RS), Prosigna® (ROR) and EndoPredict® (EP/EPclin) prognostic tests, which include some of these genes, vary according to the time in the menstrual cycle when they are measured.
Methods
Pairs of test scores were derived from 30 ER-positive/human epidermal growth factor receptor-2-negative tumours sampled at two different points of the menstrual cycle. Menstrual cycle windows were prospectively defined as either W1 (days 1–6 and 27–35; low oestrogen and low progesterone) or W2 (days 7–26; high oestrogen and high or low progesterone).
Results
The invasion module score of RS was lower (− 10.9%;
p
= 0.098), whereas the ER (+ 16.6%;
p
= 0.046) and proliferation (+ 7.3%;
p
= 0.13) module scores were higher in W2.
PGR
expression was significantly increased in W2 (+ 81.4%;
p
= 0.0029). Despite this, mean scores were not significantly different between W1 and W2 for any of the tests and the two measurements showed high correlation (
r
= 0.72–0.93). However, variability between the two measurements led to tumours being assigned to different risk categories in the following proportion of cases: RS 22.7%, ROR 27.3%, EP 13.6% and EPclin 13.6%.
Conclusion
There are significant changes during the menstrual cycle in the expression of some of the genes and gene module scores comprising the RS, ROR and EP/EPclin scores. These did not affect any of the prognostic scores in a systematic fashion, but there was substantial variability in paired measurements.
Locally advanced breast cancer (LABC) represents the most advanced stage breast cancer that is still potentially curable with surgery, radiation, and systemic therapy. The purpose of this review is ...to discuss LABC in the context of modern practice with a focus on its definition and potential consequences.
There is no one encompassing definition for this disease, but in general cancers of the breast are considered to be locally advanced if they are large and/or have infiltrated into adjacent tissues (the overlying skin or underlying muscles) and/or are found to have extensive locoregional lymph node involvement. It is not surprising, therefore, that LABC can cause significant morbidity and mortality.
Recent advances in our understanding of the biology of breast cancer have made it clear that LABC does not represent a single clinical entity but rather a heterogeneous group of breast tumors that share a common theme of extensive locoregional spread without overt evidence of distant metastatic disease. Despite advances in breast cancer screening and treatment LABC remains a significant global healthcare issue.
Objective.
To demonstrate proof of concept for a smart phone‐empowered community health worker (CHW) model of care for breast health promotion, clinical breast examination (CBE), and patient ...navigation in rural Bangladesh.
Methods.
This study was a randomized controlled trial; July 1 to October 31, 2012, 30 CHWs conducted door‐to‐door interviews of women aged 25 and older in Khulna Division. Only women who disclosed a breast symptom were offered CBE. Arm A: smart phone with applications to guide interview, report data, show motivational video, and offer appointment for women with an abnormal CBE. Arm B: smart phone/applications identical to Arm A plus CHW had training in “patient navigation” to address potential barriers to seeking care. Arm C: control arm (no smart phone; same interview recorded on paper). Outcomes are presented as the “adherence” (to advice regarding a clinic appointment) for women with an abnormal CBE. This study was approved by Women's College Hospital Research Ethics Board (Toronto, Ontario, Canada) and district government officials (Khulna, Bangladesh). Funded by Grand Challenges Canada.
Results.
In 4 months, 22,337 women were interviewed; <1% declined participation, and 556 women had an abnormal CBE. Control group CHWs completed fewer interviews, had inferior data quality, and identified significantly fewer women with abnormal breast exams compared with CHWs in arms A and B. Arm B had the highest adherence.
Conclusion.
CHWs guided by our smart phone applications were more efficient and effective in breast health promotion compared with the control group. CHW “navigators” were most effective in encouraging women with an abnormal breast examination to adhere to advice regarding clinic attendance.
Community health workers (CHWs) used smart phones with and without patient navigation to promote breast health in rural Bangladesh and were compared with CHWs using paper‐and‐pencil methods only. Findings showed that CHWs who did not use the smart phone applications completed fewer interviews, had inferior data quality, and identified significantly fewer women with abnormal breast exams, indicating that smart phones can be used to promote breast health in rural areas. CHWs with smart phones and 1‐day training in patient navigation were more effective in encouraging women with abnormal breast exams to attend for proper care.
BackgroundBreast cancer is the leading cause of female mortality in low-income and middle-income countries (LMICs). Early detection of breast cancer, either through screening or early diagnosis ...initiatives, led by community health workers (CHWs) has been proposed as a potential way to address the unjustly high mortality rates. We therefore document: (1) where and how CHWs are currently deployed in this role; (2) how CHWs are trained, including the content, duration and outcomes of training; and (3) the evidence on costs associated with deploying CHWs in breast cancer early detection.MethodsWe conducted a systematic scoping review and searched eight major databases, as well as the grey literature. We included original studies focusing on the role of CHWs to assist in breast cancer early detection in a country defined as a LMIC according to the World Bank.Findings16 eligible studies were identified. Several roles were identified for CHWs including awareness raising and community education (n=13); history taking (n=7); performing clinical breast examination (n=9); making onward referrals (n=7); and assisting in patient navigation and follow-up (n=4). Details surrounding training programmes were poorly reported and no studies provided a formal cost analysis.ConclusionsDespite the relative paucity of studies addressing the role of CHWs in breast cancer early detection, as well as the heterogeneity of existing studies, evidence suggests that CHWs can play a number of important roles in breast cancer early detection initiatives in LMICs. However, if they are to realise their full potential, they must be appropriately supported within the wider health system.
Mammographic density is one of the strongest risk factors for breast cancer. In the general population, mammographic density can be modified by various exposures; whether this is true for women a ...strong family history is not known. Thus, we evaluated the association between reproductive, hormonal, and lifestyle risk factors and mammographic density among women with a strong family history of breast cancer but no BRCA1 or BRCA2 mutation.
We included 97 premenopausal and 59 postmenopausal women (age range: 27-68 years). Risk factor data was extracted from the research questionnaire closest in time to the mammogram performed nearest to enrollment. The Cumulus software was used to measure percent density, dense area, and non-dense area for each mammogram. Multivariate generalized linear models were used to evaluate the relationships between breast cancer risk factors and measures of mammographic density, adjusting for relevant covariates.
Among premenopausal women, those who had two live births had a mean percent density of 28.8% vs. 41.6% among women who had one live birth (P=0.04). Women with a high body weight had a lower mean percent density compared to women with a low body weight among premenopausal (17.6% vs. 33.2%; P=0.0006) and postmenopausal women (8.7% vs. 14.7%; P=0.04). Among premenopausal women, those who smoked for 14 years or longer had a lower mean dense area compared to women who smoked for a shorter duration (25.3cm
vs. 53.1cm
; P=0.002). Among postmenopausal women, former smokers had a higher mean percent density (19.5% vs. 10.8%; P=0.003) and dense area (26.9% vs. 16.4%; P=0.01) compared to never smokers. After applying the Bonferroni correction, the association between body weight and percent density among premenopausal women remained statistically significant.
In this cohort of women with a strong family history of breast cancer, body weight was associated with mammographic density. These findings suggest that mammographic density may explain the underlying relationship between some of these risk factors and breast cancer risk, and lend support for the inclusion of mammographic density into risk prediction models.
It is well known that early-onset breast cancer may be due to an inherited predisposition. When evaluating women diagnosed with breast cancer under age 30, two important syndromes are typically ...considered: Hereditary Breast and Ovarian Cancer Syndrome and Li-Fraumeni syndrome. Many women are offered genetic testing for mutations in the
BRCA1
and
BRCA2
genes; however, few are offered genetic testing for mutations in the
TP53
gene. There is a concern that overly restrictive testing of
TP53
may fail to recognize families with Li-Fraumeni syndrome. We reviewed the genetic test results and family histories of all women with early-onset breast cancer who had genetic testing of the
TP53
gene at the Toronto Hospital for Sick Children. Of the 28 women tested, six (33.3 %) had a mutation in the
TP53
gene; a mutation was found in 7.7 % of women who did not meet current criteria for Li-Fraumeni syndrome. By reviewing similar data published between 2000 and 2011, we estimate that 5–8 % of women diagnosed with early-onset breast cancer, and who have a negative family history, may have a mutation in the
TP53
gene. Given the potential benefits versus harms of this testing, we discuss the option of simultaneous testing of all three genes (
BRCA1
,
BRCA2
, and
TP53
) for women diagnosed with breast cancer before age 30.
Automated Visual Examination (AVE) is a deep learning algorithm that aims to improve the effectiveness of cervical precancer screening, particularly in low- and medium-resource regions. It was ...trained on data from a large longitudinal study conducted by the National Cancer Institute (NCI) and has been shown to accurately identify cervices with early stages of cervical neoplasia for clinical evaluation and treatment. The algorithm processes images of the uterine cervix taken with a digital camera and alerts the user if the woman is a candidate for further evaluation. This requires that the algorithm be presented with images of the cervix, which is the object of interest, of acceptable quality, i.e., in sharp focus, with good illumination, without shadows or other occlusions, and showing the entire squamo-columnar transformation zone. Our prior work has addressed some of these constraints to help discard images that do not meet these criteria. In this work, we present a novel algorithm that determines that the image contains the cervix to a sufficient extent. Non-cervix or other inadequate images could lead to suboptimal or wrong results. Manual removal of such images is labor intensive and time-consuming, particularly in working with large retrospective collections acquired with inadequate quality control. In this work, we present a novel ensemble deep learning method to identify cervix images and non-cervix images in a smartphone-acquired cervical image dataset. The ensemble method combined the assessment of three deep learning architectures, RetinaNet, Deep SVDD, and a customized CNN (Convolutional Neural Network), each using a different strategy to arrive at its decision, i.e., object detection, one-class classification, and binary classification. We examined the performance of each individual architecture and an ensemble of all three architectures. An average accuracy and F-1 score of 91.6% and 0.890, respectively, were achieved on a separate test dataset consisting of more than 30,000 smartphone-captured images.
A Lancet Commission on women and cancer Ginsburg, Ophira; Horton, Richard
The Lancet (British edition),
07/2020, Letnik:
396, Številka:
10243
Journal Article
Diagnosing cancer earlier can enable timely treatment and optimize outcomes. Worldwide, national cancer control plans increasingly encompass early diagnosis programs for symptomatic patients, ...commonly comprising awareness campaigns to encourage prompt help-seeking for possible cancer symptoms and health system policies to support prompt diagnostic assessment and access to treatment. By their nature, early diagnosis programs involve complex public health interventions aiming to address unmet health needs by acting on patient, clinical, and system factors. However, there is uncertainty regarding how to optimize the design and evaluation of such interventions. We propose that decisions about early diagnosis programs should consider four interrelated components: first, the conduct of a needs assessment (based on cancer-site-specific statistics) to identify the cancers that may benefit most from early diagnosis in the target population; second, the consideration of symptom epidemiology to inform prioritization within an intervention; third, the identification of factors influencing prompt help-seeking at individual and system level to support the design and evaluation of interventions; and finally, the evaluation of factors influencing the health systems' capacity to promptly assess patients. This conceptual framework can be used by public health researchers and policy makers to identify the greatest evidence gaps and guide the design and evaluation of local early diagnosis programs as part of broader cancer control strategies.
Background:BRCA1/BRCA2 mutations are associated with an increased lifetime risk for hereditary breast and ovarian cancer (HBOC). Compared with the Western developed countries, genetic testing and ...risk assessment for HBOC in Asia are less available, thus prohibiting the appropriate surveillance, clinical strategies and cancer management. Methods: The current status of HBOC management in 14 Asian countries, including genetic counselling/testing uptakes and clinical management options, was reviewed. We analysed how economic factors, healthcare and legal frameworks, and cultural issues affect the genetic service availability in Asia. Results: In 2012, only an estimated 4,000 breast cancer cases from 14 Asian countries have benefited from genetic services. Genetic testing costs and the absence of their adoption into national healthcare systems are the main economic barriers for approaching genetic services. Training programmes, regional accredited laboratories and healthcare professionals are not readily available in most of the studied countries. A lack of legal frameworks against genetic discrimination and a lack of public awareness of cancer risk assessment also provide challenges to HBOC management in Asia. Conclusions: The Asian BRCA Consortium reports the current disparities in genetic services for HBOC in Asia and urges the policy makers, healthcare sectors and researchers to address the limitations in HBOC management.
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