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Introduction The understanding of the biology and epidemiology of, and the optimal therapeutic strategies for, breast cancer (bca) in younger women is limited. We present the rationale, design, and initial recruitment of Reducing the Burden of Breast Cancer in Young Women (ruby), a unique national prospective cohort study designed to examine the diagnosis, treatment, quality of life, and outcomes from the time of diagnosis for young women with bca. Methods Over a 4-year period at 33 sites across Canada, the ruby study will use a local and virtual recruitment model to enrol 1200 women with bca who are 40 years of age or younger at the time of diagnosis, before initiation of any treatment. At a minimum, comprehensive patient, tumour, and treatment data will be collected to evaluate recurrence and survival. Patients may opt to complete patient-reported questionnaires, to provide blood and tumour samples, and to be contacted for future research, forming the core dataset from which 4 subprojects evaluating genetics, lifestyle factors, fertility, and local management or delivery of care will be performed. Summary The ruby study will be the most comprehensive repository of data, biospecimens, and patient-reported outcomes ever collected with respect to young women with bca from the time of diagnosis, enabling research unique to that population now and into the future. This research model could be used for other oncology settings in Canada. [ABSTRACT FROM AUTHOR]

Background Women with small nonpalpable breast tumours have an excellent prognosis. The benefit of radiotherapy in this group of low-risk women is unknown. Methods A cohort of 1595 women with stages i-iii invasive breast cancer treated with breast-conserving surgery were followed for local recurrence. Using t-tests, baseline demographic data and tumour characteristics were compared for the women who had palpable (n = 1023) and mammography-detected (n = 572) breast cancers. The 15-year actuarial risk of local recurrence was estimated using a Kaplan-Meier method, stratified for adjuvant radiation therapy (yes or no), tumour palpability (palpable or not), and tumour size (=1 cm or >1 cm). Hazard ratios (hrs) and 95% confidence intervals (95% cis) were calculated using a multivariate Cox regression model. Results were considered statistically significant if 2-tailed p values were less than 0.05. Results Among women with a nonpalpable tumour, the 15-year actuarial rates of local recurrence were, respectively, 13.9% and 18.3% for those treated and not treated with adjuvant radiation therapy (hr: 0.65; 95%ci: 0.40 to 1.06; p = 0.08). Among women with small nonpalpable breast cancers (=1.0 cm), the rates were 14.6% and 13.4% respectively (p = 0.67). The absolute reduction in 15-year local recurrence was 11.0% for women with palpable tumours. Conclusions Our results suggest that women with small (<1 cm) screen-detected nonpalpable breast cancers likely derive little benefit from adjuvant radiotherapy; however, an adequately powered randomized trial would be required to make definitive conclusions. [ABSTRACT FROM AUTHOR]

The article presents questions and answers related to oncology including the appropriate age for testing, psychosocial effects of screening, and the appropriateness current cancer risk management strategies for expanded population-based screening.

The authors reflect on overdiagnosis in clinical trials for breast cancer chemoprevention. Topics include the prevetive use of antiestrogen agents, breast cancer regression, antiestrogen-based chemoprevention, the risk factors for estrogen receptor-positive breast cancers. Also discussed are methods for breast cancer diagnosis, incident breast cancers diagnosed in the clinical trials, the use of tamoxifen in chemoprevention.

Background Whether screening mammography programs should include women in their 40s is controversial. In Canada, screening of women aged 40-49 years has not been shown to reduce mortality from breast cancer. Given that screening mammography reduces mean tumour size and that tumour size is inversely associated with survival, the lack of benefit seen with screening is puzzling and suggests a possible adverse effect on mortality of mammography or subsequent treatment (or both) that counterbalances the expected benefit derived from downstaging. Methods We followed 50,436 women 40-49 years of age until age 60 for mortality from breast cancer. Of those women, one half had been randomly assigned to annual mammography and one half to no mammography. The impact of mammography on breast cancer mortality was estimated using a left-censored Cox proportional hazards model. Results Of 256 deaths from breast cancer recorded in the study cohort, 134 occurred in women allocated to mammography, and 122 occurred in those receiving usual care and not allocated to mammography. The cumulative risk of death from breast cancer to age 60 was 0.53% for women assigned to mammography and 0.48% for women not so assigned. The hazard ratiofor breast cancer-specific death associated with 1 or more screening mammograms before age 50 was 1.10 (95% confidence interval: 0.86 to 1.40). Conclusions Mammography in women 40-49 years of age is associated with a small but nonsignificant increase in the risk of dying of breast cancer before age 60. Caution should be exercised when recommending mammographic screening to women before age 50. [ABSTRACT FROM AUTHOR]

The author discusses the use of screening mammography and early detection of breast cancer. Topics include results of a 25-year Canadian National Breast Screening Study (NBSS), Siddhartha Mukherjee's book "The Emperor of All Maladies," and quality of the mammography. The author mentions the persons who criticize the NBSS including Daniel Kopans, Siddhartha Mukherjee, and Patrick Borgen.

Background It is controversial whether ductal carcinoma in situ (DCIS) is a preinvasive marker of breast cancer or if it is part of a spectrum of small cancers with malignant potential. Comparing clinical outcomes in women with invasive and noninvasive breast lesions might help to resolve the issue. Methods From a database of 2641 patients with breast cancer, we selected women who had been treated with breastconserving surgery for a cancer that was 2.0 cm or less in size, node-negative, and nonpalpable. No subject received chemotherapy. Cancers were categorized as noninvasive (stage 0, n = 172) or invasive (stage 1, n = 401) based on a review of the pathology records. We compared the actuarial risks of in-breast recurrence after invasive and noninvasive breast lesions before and after adjusting for tamoxifen and radiotherapy. Results The 18-year cumulative risk of in-breast recurrence was 35.2% for patients with dcis and 12.8% for patients with small invasive cancers (hazard ratio: 2.4; 95% confidence interval: 1.5 to 3.8; p < 0.0003). After adjustment for radiotherapy and tamoxifen treatment, the difference was small and nonsignificant (hazard ratio: 1.4; 95% confidence interval: 0.9 to 2.4; p = 0.22). Conclusions For women with small, nonpalpable, node-negative breast cancers, the likelihood of experiencing an inbreast recurrence was associated with radiotherapy and with tamoxifen, but not with the presence of cancer cells invading beyond the basement membrane. [ABSTRACT FROM AUTHOR]

Background The risk of breast cancer in carriers of BRCA1 and BRCA2 mutations is influenced by factors other than the genetic mutation itself. Modifying factors include a woman's reproductive history and family history of cancer. Risk factors are more likely to be present in women with breast cancer than in women without breast cancer, and therefore the risk of cancer in the two breasts should not be independent. It is not clear to what extent modifying factors influence the risk of a first primary or a contralateral breast cancer in BRCA carriers. Methods We conducted a matched case-control study of breast cancer among 3920 BRCA1 or BRCA2 mutation carriers. We asked whether a past history of breast cancer in the contralateral breast was a risk factor for breast cancer. Results After adjustment for age, country of residence, and cancer treatment, a previous cancer of the right breast was found to be a significant risk factor for cancer of the left breast among BRCA1 or BRCA2 carriers (relative risk: 2.1, 95% confidence interval: 1.4 to 3.0, p< 0.0001). Conclusions In a woman with a BRCA J or BRCA2 mutation who is diagnosed with breast cancer, the risk of cancer in the contralateral breast depends on the first diagnosis. That observation supports the hypothesis that there are important genetic or non-genetic modifiers of cancer risk in BRCA carriers. Discovering risk modifiers might lead to greater personalization of risk assessment and management recommendations for BRCA -positive patients. [ABSTRACT FROM AUTHOR]

Background Node-negative breast cancers from 2 cm to 5 cm in size are classified as stage II, and smaller cancers, as stage I. We sought to determine if the prognosis of women with a breast cancer exactly 2 cm in size more closely resembles that of women with a stage I or a stage II breast cancer. Methods Using a cohort of 4265 young women with breast cancer, we compared the 10-year breast cancer mortality rates for women who had a tumour 0.1-1.9 cm, exactly 2.0 cm, and 2.1-2.9 cm. Results In the first 3 years after diagnosis, the survival pattern of women with a 2.0-cm breast cancer was nearly identical to that of women with a larger cancer (2.1-3.0 c:m). From year 3 to year 10, the relative survival of women with a 2.0-cm breast cancer was improved and nearly identical to that of women with a smaller cancer. The 10-year survival rate was 89.3% for women with tumours less than 20 mm, 86.1% for women with tumours equal to 20 mm, and 8 1.2% for women with 21-mm to 29-mm tumours. Conclusions For young women with small breast cancers, the relative mortality from breast cancer is dynamic with increasing tumour size and varies with time from diagnosis. [ABSTRACT FROM AUTHOR]

Background The benefit of early detection of breast cancer is assumed to be achieved primarily by identifying disease before it has spread beyond the breast. In support of early detection, the survival experience of women with breast cancer decreases as the mean size of the cancer increases. It is not clear if women with regional spread (node-positive breast cancer) benefit from early detection to the same extent that women with node-negative breast cancer do. Methods A review was conducted of the survival experience of 1894 patients with invasive breast cancers 5.0 cm or less in size. Cases were divided into node-positive and node-negative, and tumours were categorized by size (0.1-1.0 cm, 1.1-2.0 cm, and 2.1-5.0 cm). After a mean follow-up of 9.9 years, 368 cancer-specific deaths had occurred in the cohort. The effect of tumour size on 15-year survival for subgroups of women with nodepositive and node-negative breast cancer was estimated. Results Tumour size was a strong predictor of 15-year survival in both the node-positive and node-negative cancer subgroups. A decline of 1.0 cm in size was associated with a reduction in 15-year mortality of 10.3% in the node-positive group and of 2.5% in the node-negative group. A decline of approximately 1.5 cm was associated with a reduction in mortality of 23.0% in the node-positive group and of 10.8% in the node-negative group. Conclusions The impact of decreasing tumour size on 15-year survival is much greater for women with node-positive than for women with node-negative breast cancers. Contrary to expectation, the benefit of screening is likely to be greater for women with relatively advanced breast cancer than for women with earlystage disease. [ABSTRACT FROM AUTHOR]

Background After an initial diagnosis of breast cancer, the risk of contralateral breast cancer is approximately 0.5% per year. Annual mammography is recommended to identify local recurrences and contralateral new primaries. Because the sensitivity of mammography tends to be lower in younger women, we conducted a retrospective review of the method of detection and pathologic stage of metachronous contralateral primary breast cancers according to age at diagnosis in a cohort of breast cancer patients. Methods The Henrietta Banting Database contains information on cases of breast cancer diagnosed at Women's College Hospital from 1987 to 2004. From among 1992 women in the database, 71 patients were identified who were initially diagnosed before age 60 and who subsequently developed a contralateral breast cancer. Medical records were obtained for 53 of the 71 patients. Results Of the 53 contralateral cancers, 33 (62%) were detected by mammography, including 4 in 16 patients (25%) diagnosed before age 50 and 29 in 37 patients (78%) diagnosed at age 50 or older (p ⩽ 0.001). Conclusions Mammography has poor sensitivity for the surveillance of contralateral breast cancer in early-onset breast cancer patients. Other imaging modalities should be evaluated in this setting. [ABSTRACT FROM AUTHOR]

The author discusses recurrence of ovarian cancer in women. Topics discussed include an approval olaparib for the treatment of recurrent ovarian cancer in women by the U.S. Food and Drug Administration; the cost of olaparib which is estimated 3000 U.S. dollars per month; and the need to improve research in ovarian cancer for improving the cure rate.

The article presents the author's views on the implementation of salpingectomy to prevent ovarian cancer. He comments that salpingectomy is not a bad idea for a woman with a bilateral mastectomy and no prior breast cancer but again, this question is difficult to study. He remarks that the degree of protection offered by salpingectomy alone.

The authors reflect on the treatment options available for women with breast cancer risks at intermediate levels. They mention tamoxifen and mammography as the common options for women as of 2012. However, they say that some patients are hesitant to use tamoxifen due to its side effects. They suggest that the combination of these treatments might be beneficial.

The authors urge medical writers and editors to reduce the use of acronyms in the medical literature. They talk about the conventional wisdom behind the rationale for acronyms according to a study by H. Y. Kressel and colleagues, the reason acronyms are praised by some writers, and the most commonly cited reason for using acronyms.

The author discusses aspects of breast and ovarian cancer. He mentions an experiment that was done by collecting various deoxyribonucleic acids (DNAs) which gave a discovery to one new gene called as PPM1D (p53-inducible protein phosphate) which was found in 18 of 6912 women suffering from breast cancer and 12 of 1121 women suffering from ovarian cancer.

The article discusses the topic about bilateral cancers, and explores if it is hereditary. He notes that some bilateral cases are hereditary and cites retinoblastoma as a classic example where a child is diagnosed with the disease, then the child would likely carries a mutation in Rb1. The author says that mutated cancer susceptibility genes may increase to bilateral cancers to people who inherit a mutation.

The author reflects on the methods for assigning stages in breast cancer. He discusses the basis of different stages of breast cancer such as the stage IV which is based from metastatic disease presence at diagnosis and stages I-III that are based from tumour size and lymph nodes involvement. He cites that the changes in stage distributions over time and country marks the screening advancements. He adds that staging is beneficial when patients are grouped based from tumour size and prognosis.

The author reflects on the offering of the BreastNext genetic test by California-based Ambry Genetics for women with familial breast cancer in February 2012. He agrees the need of testing for CHEK2 gene mutations, but he believes that the examination for additional 13 genes in the BreastNext panel is not yet justified. He suggests to sequence several families of breast cancer patients who meet the company's criteria to assess the prevalence of gene mutations.

The author discusses the anticipative and cohort effect issues of breast cancer (BRCA) carriers at early age. The author denotes several research studies regarding the decline of BRCA mutation. The author cites the difference between anticipation and cohort effect in terms of gene penetrance. The author also mentions the factor of nuclear pedigrees of BRCA within the female members of the family.

The author offers views on the early-onset risk of breast cancer. The author is particular on the study which indicated that the risk of primary breast cancer increase monotonically with age while its collateral risks decreases throughout life. The author adds that the risk can be compared to the magnitude of risks of breast cancers attributable to mutation in BRCA1, BRCA2, and TP53.

The author discusses increasing breast cancer deaths and the need to screening cancer to prevent cancer mortality and offers the Canadian National Breast Screening Study on the breast cancer-specific death.