Risk of distant recurrence (DR) among women with estrogen receptor (ER) -positive early breast cancer is the major determinant of recommendations for or against chemotherapy. It is frequently ...estimated using the Oncotype DX recurrence score (RS). The PAM50 risk of recurrence (ROR) score provides an alternative approach, which also identifies intrinsic subtypes.
mRNA from 1,017 patients with ER-positive primary breast cancer treated with anastrozole or tamoxifen in the ATAC trial was assessed for ROR using the NanoString nCounter. Likelihood ratio (LR) tests and concordance indices (c indices) were used to assess the prognostic information provided beyond that of a clinical treatment score (CTS) by RS, ROR, or IHC4, an index of DR risk derived from immunohistochemical assessment of ER, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and Ki67.
ROR added significant prognostic information beyond CTS in all patients (Δ LR-χ(2) = 33.9; P < .001) and in all four subgroups: node negative, node positive, HER2 negative, and HER2 negative/node negative; more information was added by ROR than by RS. C indices in the HER2-negative/node-negative subgroup were 0.73, 0.76, and 0.78 for CTS, CTS plus RS, and CTS plus ROR, respectively. More patients were scored as high risk and fewer as intermediate risk by ROR than by RS. Relatively similar prognostic information was added by ROR and IHC4 in all patients but more by ROR in the HER2-negative/node-negative group.
ROR provides more prognostic information in endocrine-treated patients with ER-positive, node-negative disease than RS, with better differentiation of intermediate- and higher-risk groups.
This paper summarises the position of ESGO and EFC on cervical screening based on existing guidelines and opinions of a team of lead experts. HPV test is replacing cytology as this offers greater ...protection against cervical cancer and allows longer screening intervals. Only a dozen of HPV tests are considered as clinically validated for screening. The lower specificity of HPV test dictates the use of triage tests that can select women for colposcopy. Reflex cytology is currently the only well validated triage test; HPV genotyping and p16 immunostaining may be used in the future, although methylation assays and viral load also look promising. A summary of quality assurance benchmarks is provided, and the importance to audit the screening histories of women who developed cancer is noted as a key objective. HPV-based screening is more cost-effective than cytology or cotesting. HPV-based screening should continue in the post-vaccination era. Only a fraction of the female population is vaccinated, and this varies across countries. A major challenge will be to personalise screening frequency according to vaccination status. Still the most important factor for successful prevention by screening is high population coverage and organised screening. Screening with self-sampling to reach under-screened women is promising.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
There is little consensus, and minimal evidence, regarding the age at which to stop cervical screening. We studied the association between screening at age 50-64 y and cervical cancer at age 65-83 y.
...Cases were women (n = 1,341) diagnosed with cervical cancer at age 65-83 y between 1 April 2007 and 31 March 2012 in England and Wales; age-matched controls (n = 2,646) were randomly selected from population registers. Screening details from 1988 onwards were extracted from national databases. We calculated the odds ratios (OR) for different screening histories and subsequent cervical cancer. Women with adequate negative screening at age 65 y (288 cases, 1,395 controls) were at lowest risk of cervical cancer (20-y risk: 8 cancers per 10,000 women) compared with those (532 cases, 429 controls) not screened at age 50-64 y (20-y risk: 49 cancers per 10,000 women, with OR = 0.16, 95% CI 0.13-0.19). ORs depended on the age mix of women because of the weakening association with time since last screen: OR = 0.11, 95% CI 0.08-0.14 at 2.5 to 7.5 y since last screen; OR = 0.27, 95% CI 0.20-0.36 at 12.5 to 17.5 y since last screen. Screening at least every 5.5 y between the ages 50 and 64 y was associated with a 75% lower risk of cervical cancer between the ages 65 and 79 y (OR = 0.25, 95% CI 0.21-0.30), and the attributable risk was such that in the absence of screening, cervical cancer rates in women aged 65+ would have been 2.4 (95% CI 2.1-2.7) times higher. In women aged 80-83 y the association was weaker (OR = 0.49, 95% CI 0.28-0.83) than in those aged 65-69 y (OR = 0.12, 95% CI 0.09-0.17). This study was limited by an absence of data on confounding factors; additionally, findings based on cytology may not generalise to human papillomavirus testing.
Women with adequate negative screening at age 50-64 y had one-sixth of the risk of cervical cancer at age 65-83 y compared with women who were not screened. Stopping screening between ages 60 and 69 y in women with adequate negative screening seems sensible, but further screening may be justifiable as life expectancy increases.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective The objective of the study was to compare 9 cervical cancer screening strategies to the current screening standard (cytology with human papillomavirus HPV triage of atypical squamous cells ...of undetermined significance) for the detection of high-grade cervical disease. Study Design Women (n = 34,254) aged 30 years or older from the Addressing the Need for Advanced HPV Diagnostics (ATHENA) study underwent screening with cytology and HPV testing with simultaneous HPV16/18 genotyping; those with atypical squamous cells of undetermined significance cytology or greater or HPV-positive status were referred for colposcopy. Results In general, screening strategies that offered greater sensitivity also required more referral to colposcopy. HPV testing was more sensitive than cytology for detection of cervical intraepithelial neoplasia grade 2 or greater, but strategies that depended on cytology for triage of HPV-positive women decreased this sensitivity. Various strategies of cotesting with cytology increased sensitivity but did so by increasing testing. Strategies that included integrated HPV16/18 testing provided more efficient referral to colposcopy. Conclusion Strategies that maximize detection of women at greatest risk of cervical intraepithelial neoplasia grade 3 or greater by immediate referral to colposcopy, with follow-up testing of women at intermediate risk, maximize the benefits of cervical cancer screening while decreasing the potential harm. Incorporating screening with HPV and triage of HPV-positive women by a combination of genotyping for HPV16/18 and cytology provided a good balance between maximizing sensitivity (benefit) and specificity by limiting the number of colposcopies (potential harm).
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Worldwide, there are several approaches for the prevention of cervical cancer, and in the near future it is likely that human papillomavirus (HPV) vaccination and HPV-based screening will be ...complementary strategies. In the US, professional guidelines on HPV screening recommend a co-testing approach utilizing HPV DNA testing and cytology in women aged ≥ 30 years. However, a growing body of evidence indicates that HPV testing is more sensitive than cytology, suggesting that HPV DNA testing may be more useful as the sole primary screening modality, especially for newly implemented programs. HPV vaccination programs targeted at young girls have been widely implemented in several affluent countries, and currently available data confirm the long-term efficacy of the VLP-based vaccines against HPV-related disease over periods of up to 8 years. If these HPV vaccines continue to demonstrate sustained and durable efficacy, less frequent screening may become a reality, but screening will continue to play an important role in providing protection for disease caused by types not included in these vaccines. However, a significant HPV vaccination-induced reduction in cervical cancer burden is not likely to be realized for at least 10 to 15 years.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
16.
Preventive therapy for cancer Cuzick, Jack
The lancet oncology,
August 2017, 2017-08-00, 20170801, Volume:
18, Issue:
8
Journal Article
Peer reviewed
Therapeutic cancer prevention is a developing area that can gain a lot from the successes in the prevention of cardiovascular diseases. Although weight control and physical activity are important in ...the prevention of both diseases, several other preventive measures exist. Low-dose aspirin for cancer prevention is often cited as the most important approach in terms of population benefit, and should be offered to those older than 50 years of age without hypertension or risk factors for gastrointestinal bleeding. Universal vaccination against the human papillomavirus, ideally with the nine-valent vaccine, also offers substantial benefits for the whole population if given before infection occurs (ie, typically at age 12–14 years). Other therapies, such as anti-oestrogen drugs for breast cancer prevention, should be targeted to high-risk groups to maintain a favourable benefit–risk ratio. Better algorithms for identification and improved platforms to reach these groups, such as during a screening visit, remain a key priority to allow existing knowledge to inform public health. Many other promising compounds have been identified, often as components of food, but results suggesting increased disease incidence with β carotene and vitamin E administration indicate that such treatments need rigorous evaluation before acceptance.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Summary Background When the mechanism of action behind treatment toxicity reflects the intended effect on the treatment target, the toxicity might be a useful marker for efficacy. During endocrine ...treatment of breast cancer, the occurrence of symptoms related to oestrogen depletion or oestrogen blockade might thus be a predictor of treatment effectiveness. In this retrospective analysis, the relation between the reported incidence of vasomotor or joint symptoms and breast cancer recurrence in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial is assessed. Methods Women with hormone-receptor-positive tumours who reported vasomotor or joint symptoms at the first follow-up visit (3 months) in the ATAC trial, (which assessed tamoxifen or anastrozole for adjuvant treatment of postmenopausal breast cancer), were compared with women without these symptoms to see if there was a relation between these symptoms and subsequent recurrence. The ATAC trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN18233230. Findings 1486 of 3964 (37·5%) eligible women reported newly emergent vasomotor symptoms at the 3-month follow-up visit and had lower subsequent recurrence than those who did not report these symptoms (223 during 10 752 women-years of follow-up vs 366 during 11 573 woman-years of follow-up, respectively; hazard ratio HR 0·84 95% CI 0·71–1·00, p=0·04; adjusted for age, body-mass index, previous hormone-replacement therapy, nodal status, tumour size, and tumour grade). A greater decrease in breast-cancer recurrence was seen for the 1245 of 3964 (31·4%) eligible women who reported new joint symptoms at the 3-month follow-up visit compared with those not reporting these symptoms (158 during 9242 women-years of follow-up vs 366 during 11 573 women-years of follow-up; adjusted HR 0·60 0·50–0·72, p<0·0001). Interpretation The appearance of new vasomotor symptoms or joint symptoms within the first 3 months of treatment is a useful biomarker, suggesting a greater response to endocrine treatment compared with women without these symptoms. Awareness of the relation between early treatment-emergent symptoms and beneficial response to therapy might be useful when reassuring patients who present with them, and might help to improve long-term treatment adherence when symptoms cannot be alleviated effectively. Funding Cancer Research UK and AstraZeneca.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Adjuvant endocrine therapy beyond 5 years reduces recurrence in patients with estrogen receptor-positive breast cancer. We have previously shown that immunohistochemical markers (IHC4) and two gene ...expression profile tests (recurrence score RS and PAM50 risk of recurrence ROR) are associated with time to distant recurrence, and we have now assessed the value of each of these scores and routine clinical variables for predicting outcome, specifically in years 5 to 10.
We used univariate and multivariable proportional hazards models to determine the prognostic value of all variables and scores (IHC4, RS, ROR) for distant recurrence, separately in years 0 to 5 and specifically for years 5 to 10 for all patients. All statistical tests were two-sided.
Nodal status and tumor size were at least as strong in years 5 to 10 as in years 0 to 5 (nodal status, years 5-10: χ² = 21.72 vs years 0-5: χ² = 11.08, both P < .001; tumor size, years 5-10: χ² = 10.52 vs years 0-5: χ² = 10.82, both P = .001). Ki67 and the overall IHC4 score were the only statistically significant biomarkers related to distant recurrence univariablely in the 5 to 10 year period (χ² = 8.67, χ² = 13.22, respectively). The ROR score was the strongest molecular prognostic factor in the late follow-up period (χ² = 16.29; P < .001), whereas IHC4 (χ² = 7.41) and RS (χ² = 5.55) were only weakly prognostic in this period. Similar results were seen for all subgroups and for all recurrences.
None of the IHC4 markers provided statistically significant prognostic information in years 5 to 10, except for nodal status and tumor size. ROR gave the strongest prognostic information in years 5 to 10. These results may help select patients who could benefit most from hormonal therapy beyond 5 years of treatment.
Summary Background Aromatase inhibitors effectively prevent breast cancer recurrence and development of new contralateral tumours in postmenopausal women. We assessed the efficacy and safety of the ...aromatase inhibitor anastrozole for prevention of breast cancer in postmenopausal women who are at high risk of the disease. Methods Between Feb 2, 2003, and Jan 31, 2012, we recruited postmenopausal women aged 40–70 years from 18 countries into an international, double-blind, randomised placebo-controlled trial. To be eligible, women had to be at increased risk of breast cancer (judged on the basis of specific criteria). Eligible women were randomly assigned (1:1) by central computer allocation to receive 1 mg oral anastrozole or matching placebo every day for 5 years. Randomisation was stratified by country and was done with blocks (size six, eight, or ten). All trial personnel, participants, and clinicians were masked to treatment allocation; only the trial statistician was unmasked. The primary endpoint was histologically confirmed breast cancer (invasive cancers or non-invasive ductal carcinoma in situ). Analyses were done by intention to treat. This trial is registered, number ISRCTN31488319. Findings 1920 women were randomly assigned to receive anastrozole and 1944 to placebo. After a median follow-up of 5·0 years (IQR 3·0–7·1), 40 women in the anastrozole group (2%) and 85 in the placebo group (4%) had developed breast cancer (hazard ratio 0·47, 95% CI 0·32–0·68, p<0·0001). The predicted cumulative incidence of all breast cancers after 7 years was 5·6% in the placebo group and 2·8% in the anastrozole group. 18 deaths were reported in the anastrozole group and 17 in the placebo group, and no specific causes were more common in one group than the other (p=0·836). Interpretation Anastrozole effectively reduces incidence of breast cancer in high-risk postmenopausal women. This finding, along with the fact that most of the side-effects associated with oestrogen deprivation were not attributable to treatment, provides support for the use of anastrozole in postmenopausal women at high risk of breast cancer. Funding Cancer Research UK, the National Health and Medical Research Council Australia, Sanofi-Aventis, and AstraZeneca.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
PDF
