Results of two large case–control studies that analyzed the associations between a number of putative cancer susceptibility genes and breast cancer risk are now reported in the
Journal
. The study by ...Dorling et al.
1
included 34 genes and 113,000 women from 25 countries, and the study by Hu et al.
2
included 28 genes and 64,000 women from the United States. Variants in 8 genes —
BRCA1
,
BRCA2
,
PALB2
,
BARD1
,
RAD51C
,
RAD51D
,
ATM
, and
CHEK2
— had a significant association with breast cancer risk in both studies. In addition, there was a significant association for variants in
MSH6
in the international . . .
Background
In patients with breast cancer, increasing tumour size at diagnosis is associated with an increased likelihood of axillary lymph node involvement and increased breast cancer-specific ...mortality. However, this relation is based on studies which combine all tumours smaller than 1.0 cm in a single category and all tumours larger than 5.0 cm in another category. This coarse classification may obscure a nuanced description of the effects of tumour size across the full range of possible sizes.
Methods
We examined the relationship between primary tumour size, lymph node status and distant metastases in a cohort of 819,647 women diagnosed with first primary invasive breast cancer from 1990 to 2014 in the Surveillance, Epidemiology and End Results (SEER) registries database. All patients in the cohort had a known primary tumour size between 1 and 150 mm in greatest dimension. Primary tumour size was examined as a continuous (1–150 mm) and categorical variable (15 size groups; 10-mm intervals). For each 1- or 10-mm size group, we determined the proportion of patients with positive lymph nodes at diagnosis, the proportion of patients with distant metastases at diagnosis and the actuarial cumulative risk of breast cancer-specific mortality at 15 years from diagnosis.
Results
Among 819,647 patients with invasive breast tumours between 1 and 150 mm in size, there was a non-linear correlation between increasing tumour size and the prevalence of lymph node metastases at diagnosis (% node-positive), the prevalence of distant metastases at diagnosis (% stage IV) and the 15-year rate of breast cancer-specific mortality across the entire size spectrum. For very small tumours (under 10 mm) and for very large tumours (larger than 60–90 mm) there was little correlation between tumour size and metastasis risk.
Conclusions
The relationship between tumour size, lymph node status and distant metastases in patients with invasive breast cancer is not linear. This calls into question the conventional model that the capacity for a primary breast tumour to metastasize increases as the tumour enlarges.
Breast cancer in young women Narod, Steven A
Nature reviews. Clinical oncology,
08/2012, Letnik:
9, Številka:
8
Journal Article
Recenzirano
About one in 300 women will be diagnosed with breast cancer before the age of 40. Advances in screening have not had an impact on mortality in women who are too young to be candidates for screening. ...Risk factors for early breast cancer include a lean body habitus and recent use of an oral contraceptive. Breast cancers in very young women are typically aggressive, in part owing to the over-representation of high-grade, triple-negative tumours, but young age is an independent negative predictor of cancer-specific survival. Very early age-of-onset also correlates strongly with the risk of local recurrence and with the odds of contralateral breast cancer. Given the high risks of local and distant recurrence in young women with invasive breast cancer, most (if not all) young patients are candidates for chemotherapy. It is hoped that by increasing breast cancer awareness, the proportion of invasive breast cancers that are diagnosed at 2.0 cm or smaller will increase and that this will lead to a reduction in mortality.
IMPORTANCE: Women with early-stage breast cancers are expected to have excellent survival rates. It is important to identify factors that predict diagnosis of early-stage breast cancers. OBJECTIVE: ...To determine the proportion of breast cancers that were identified at an early stage (stage I) in different racial/ethnic groups and whether ethnic differences may be better explained by early detection or by intrinsic biological differences in tumor aggressiveness. DESIGN, SETTING, AND PARTICIPANTS: Observational study of women diagnosed with invasive breast cancer from 2004 to 2011 who were identified in the Surveillance, Epidemiology, and End Results (SEER) 18 registries database (N = 452 215). For each of 8 racial/ethnic groups, biological aggressiveness (triple-negative cancers, lymph node metastases, and distant metastases) of small-sized tumors of 2.0 cm or less was estimated. The odds ratio (OR) for being diagnosed at stage I compared with a later stage and the hazard ratio (HR) for death from stage I breast cancer by racial/ethnic group were determined. The date of final follow-up was December 31, 2011. MAIN OUTCOMES AND MEASURES: Breast cancer stage at diagnosis and 7-year breast cancer–specific survival, adjusted for age at diagnosis, income, and estrogen receptor status. RESULTS: Of 373 563 women with invasive breast cancer, 268 675 (71.9%) were non-Hispanic white; 34 928 (9.4%), Hispanic white; 38 751 (10.4%), black; 25 211 (6.7%), Asian; and 5998 (1.6%), other ethnicities. Mean follow-up time was 40.6 months (median, 38 months). Compared with non-Hispanic white women diagnosed with stage I breast cancer (50.8%), Japanese women (56.1%) were more likely to be diagnosed (OR, 1.23 95% CI, 1.15-1.31, P < .001) and black women (37.0%) were less likely to be diagnosed (OR, 0.65 95% CI, 0.64-0.67, P < .001). Actuarial risk of death from stage I breast cancer at 7 years was higher among black women (6.2%) than non-Hispanic white women (3.0%) (HR, 1.57 95% CI, 1.40-1.75; P < .001), and lower among South Asian women (1.7%) (HR, 0.48 95% CI, 0.20-1.15; P = .10). Black women were more likely to die of breast cancer with small-sized tumors (9.0%) than non-Hispanic white women (4.6%) (HR, 1.96 95% CI, 1.82-2.12; P < .001); the difference remained after adjustment for income and estrogen receptor status (HR, 1.56 95% CI, 1.45-1.69; P < .001). CONCLUSIONS AND RELEVANCE: Among US women diagnosed with invasive breast cancer, the likelihood of diagnosis at an early stage, and survival after stage I diagnosis, varied by race and ethnicity. Much of the difference could be statistically accounted for by intrinsic biological differences such as lymph node metastasis, distant metastasis, and triple-negative behavior of tumors.
It has been suggested that a personalised approach to cancer prevention and screening might lead to a new paradigm for cancer control. Various aspects include testing for high-penetrance cancer ...susceptibility genes and generating personal risks scores, based on panels of single nucleotide polymorphisms. These tests can categorize women into various groupings of risk for cancer prevention (surgery and chemoprevention) cancer screening and prevention of cancer recurrence. In this review, I investigate various claims and come to the conclusion that the approach may be beneficial for the occasional patient but is unlikely to have any impact on reducing the burden of cancer incidence and mortality as whole. Challenges include meeting a high uptake of the test in the population, developing an effective and acceptable intervention and the willingness of healthy women to follow health care provider recommendations. The review focuses on strategies to reduce mortality from breast and ovarian cancer but is potentially applicable to other cancer sites, such as colon, prostate, and endometrial.
Ovarian cancer is the second most lethal gynecological malignancy. The tumour biomarker CA125 has been used as the primary ovarian cancer marker for the past four decades. The focus on diagnosing ...ovarian cancer in stages I and II using CA125 as a diagnostic biomarker has not improved patients' survival. Therefore, screening average-risk asymptomatic women with CA125 is not recommended by any professional society. The dualistic model of ovarian cancer carcinogenesis suggests that type II tumours are responsible for the majority of ovarian cancer mortality. However, type II tumours are rarely diagnosed in stages I and II. The recent shift of focus to the diagnosis of low volume type II ovarian cancer in its early stages of evolution provides a new and valuable target for screening. Type II ovarian cancers are usually diagnosed in advanced stages and have significantly higher CA125 levels than type I tumours. The detection of low volume type II carcinomas in stage IIIa/b is associated with a higher likelihood for optimal cytoreduction, the most robust prognostic indicator for ovarian cancer patients. The diagnosis of type II ovarian cancer in the early substages of stage III with CA125 may be possible using a higher cutoff point rather than the traditionally used 35 U/mL through the use of point-of-care CA125 assays in primary care facilities. Rapid point-of-care testing also has the potential for effective longitudinal screening and quick monitoring of ovarian cancer patients during and after treatment. This review covers the role of CA125 in the diagnosis and management of ovarian cancer and explores novel and more effective screening strategies with CA125.
Genetic testing for BRCA1 and BRCA2 mutations is gaining acceptance in clinical oncology worldwide and may help target unaffected high-risk women for prevention and for close surveillance. Annual ...screening with MRI seems to be an effective surveillance strategy, but the long term follow-up of women with small MRI-detected breast cancers is necessary to establish its ultimate value. Women with cancer and a BRCA mutation may benefit from tailored treatments, such as cisplatin or olaparib. The treatment goals for a woman with a BRCA-associated breast cancer should be to prevent recurrence of the initial cancer and to prevent second primary breast and ovarian cancers. Mutations in BRCA1 and BRCA2 are presented throughout the world and it is important that the benefits of genetic testing and of targeted therapies be extended to women who live outside of North America and Western Europe.
Women with ductal carcinoma in situ (DCIS), or stage 0 breast cancer, often experience a second primary breast cancer (DCIS or invasive), and some ultimately die of breast cancer.
To estimate the 10- ...and 20-year mortality from breast cancer following a diagnosis of DCIS and to establish whether the mortality rate is influenced by age at diagnosis, ethnicity, and initial treatment received.
Observational study of women who received a diagnosis of DCIS from 1988 to 2011 in the Surveillance, Epidemiology, and End Results (SEER) 18 registries database. Age at diagnosis, race/ethnicity, pathologic features, date of second primary breast cancer, cause of death, and survival were abstracted for 108,196 women. Their risk of dying of breast cancer was compared with that of women in the general population. Cox proportional hazards analysis was performed to estimate the hazard ratio (HR) for death from DCIS by age at diagnosis, clinical features, ethnicity, and treatment.
Ten- and 20-year breast cancer-specific mortality.
Among the 108 196 women with DCIS, the mean (range) age at diagnosis of DCIS was 53.8 (15-69) years and the mean (range) duration of follow-up was 7.5 (0-23.9) years. At 20 years, the breast cancer-specific mortality was 3.3% (95% CI, 3.0%-3.6%) overall and was higher for women who received a diagnosis before age 35 years compared with older women (7.8% vs 3.2%; HR, 2.58 95% CI, 1.85-3.60; P < .001) and for blacks compared with non-Hispanic whites (7.0% vs 3.0%; HR, 2.55 95% CI, 2.17-3.01; P < .001). The risk of dying of breast cancer increased after experience of an ipsilateral invasive breast cancer (HR, 18.1 95% CI, 14.0-23.6; P < .001). A total of 517 patients died of breast cancer following a DCIS diagnosis (mean follow-up, 7.5 range, 0-23.9 years) without experiencing an in-breast invasive cancer prior to death. Among patients who received lumpectomy, radiotherapy was associated with a reduction in the risk of ipsilateral invasive recurrence at 10 years (2.5% vs 4.9%; adjusted HR, 0.47 95% CI, 0.42-0.53; P < .001) but not of breast cancer-specific mortality at 10 years (0.8% vs 0.9%; HR, 0.86 95% CI, 0.67-1.10; P = .22).
Important risk factors for death from breast cancer following a DCIS diagnosis include age at diagnosis and black ethnicity. The risk of death increases after a diagnosis of an ipsilateral second primary invasive breast cancer, but prevention of these recurrences by radiotherapy does not diminish breast cancer mortality at 10 years.
Background
Ductal carcinoma in situ (DCIS) is a neoplastic proliferation of epithelial cells which is confined within the basement membrane of the mammary ductal–lobular system. It is of interest to ...determine to what extent the potential to metastasize increases for DCIS patients when the basement membrane is breached (i.e. microinvasion is present).
Methods
We retrieved the records of 525,395 women who had either first primary DCIS or small (≤ 2.0 cm) node-negative invasive breast cancer in the Surveillance, Epidemiology and End Results (SEER) registries database (1990–2013). For each patient, we extracted information on year of diagnosis, age at diagnosis, tumour size, tumour grade, oestrogen receptor status, use of radiotherapy, type of surgery, cause of death and follow-up time. We classified patients into four groups, according to the size of the invasive component of the primary tumour. We estimated the actuarial rate of breast cancer-specific mortality at ten and 20 years for women in each size category.
Results
We identified 161,394 women with pure DCIS, 13,489 women with microinvasive carcinoma (≤ 0.1 cm of invasion), 153,856 women with invasive cancer 0.2–1.0 cm in size and 196,656 women with invasive cancer 1.1–2.0 cm in size. The 20-year actuarial breast cancer-specific mortality rate was 3.8% for women with pure DCIS, was 6.9% for women with microinvasive carcinoma, was 6.8% for women with invasive cancer 0.2–1.0 cm in size and was 12.1% for women with invasive cancer 1.1–2.0 cm in size. The adjusted hazard ratio for death associated with microinvasive carcinoma (vs. pure DCIS) was 2.00 (95% CI 1.76–2.26;
p
< 0.0001).
Conclusions
In terms of prognosis, microinvasive cancer more closely resembles small invasive cancer 0.2–1.0 cm) than pure DCIS. For invasive cancers under 1.0 cm, size has little impact on mortality.
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