Marta Román

Women treated with breast conserving surgery do better than those with mastectomy independent of detection mode, prognostic and predictive tumor characteristics

BACKGROUND Primary breast conserving treatment (BCT) is well known to have similar long-term survival as mastectomy in breast cancer patients. However, recent studies are suggesting better survival among women treated with BCT compared with mastectomy. More knowledge is needed to understand how disease specific survival is influenced by detection mode, prognostic and predictive tumor characteristics. We aimed to investigate this issue among women targeted by the Norwegian Breast Cancer Screening Program. METHOD Information about 9547 women aged 50-69 years diagnosed with primary invasive breast cancer without distant metastasis, who underwent either BCT or mastectomy, 2005-2011, were included in the study. Kaplan-Meier plots were used to estimate six years survival, while Cox proportional hazards models were used to estimate the hazard ratio (HR) of breast cancer death associated with surgical treatment. Information about molecular subtype, detection mode, age at diagnosis, tumor size, lymph node involvement, and histologic grade, in addition to radiation treatment, chemotherapy and endocrine therapy were included in adjusted analyses. RESULTS BCT was performed among 61.9% of the women included in the study. Women treated with BCT had prognostic and predictive favorable tumor characteristics compared to women treated with mastectomy. Adjusted analyses revealed a 1.7 (95% CI: 1.3-2.4) higher risk of breast cancer death among women who underwent mastectomy compared with BCT. CONCLUSION Women treated with BCT have significantly better breast cancer-specific survival and a lower risk of dying from breast cancer compared to women treated with mastectomy, independent of detection mode, prognostic and predictive tumor characteristic.

Postmenopausal hormone therapy and the risk of breast cancer in Norway

There is convincing evidence that combined estrogen–progestin therapy (EPT) increases the risk of breast cancer. However, the effect of different formulations, preparations and routes of administration is largely unknown. Estrogen only‐therapy (ET) is, in general, not associated or weakly associated with breast cancer risk. We investigated the effect of hormone therapy (HT) with ET, EPT, and tibolone on risk of invasive breast cancer. Information on HT use was obtained from the Norwegian Prescription Database, and breast cancer incidence from the Cancer Registry of Norway. Poisson regression was used to estimate the incidence rate ratios (RR). We analyzed data from 686,614 Norwegian women, aged 45–79 years in January 2004, followed until December 2008, of whom 178,383 (26%) were prescribed HT. During the average 4.8 years of follow‐up, 7,910 invasive breast cancers were registered. Compared with nonusers, current users of estradiol–norethisterone acetate (NETA)(EPT) had a RR of 2.74 (95% CI: 2.55–2.95). Users of the high dose estradiol–NETA formulation Kliogest® had a RR of 3.26 (95% CI: 2.84–3.73), while users of the low dose Activelle® had a RR of 2.76 (95% CI: 2.51–3.04). Current users of tibolone had a RR of 1.91 (95% CI: 1.61–2.28). Current users of ET with oral or transdermal estradiol had a RR of 1.40 (95% CI: 1.16–1.68), and 1.40 (95% CI: 1.00–1.95), respectively. The increased incidence rates approximates one extra invasive breast cancer case diagnosed for every 259 women using estradiol–NETA for one year, and one extra case for every 475 women using tibolone. In conclusion, use of estradiol–NETA and tibolone preparations is associated with an increased breast cancer risk.

Risk of breast cancer after false-positive results in mammographic screening.

Women with false‐positive results are commonly referred back to routine screening. Questions remain regarding their long‐term outcome of breast cancer. We assessed the risk of screen‐detected breast cancer in women with false‐positive results. We conducted a joint analysis using individual level data from the population‐based screening programs in Copenhagen and Funen in Denmark, Norway, and Spain. Overall, 150,383 screened women from Denmark (1991–2008), 612,138 from Norway (1996–2010), and 1,172,572 from Spain (1990–2006) were included. Poisson regression was used to estimate the relative risk (RR) of screen‐detected cancer for women with false‐positive versus negative results. We analyzed information from 1,935,093 women 50–69 years who underwent 6,094,515 screening exams. During an average 5.8 years of follow‐up, 230,609 (11.9%) women received a false‐positive result and 27,849 (1.4%) were diagnosed with screen‐detected cancer. The adjusted RR of screen‐detected cancer after a false‐positive result was 2.01 (95% CI: 1.93–2.09). Women who tested false‐positive at first screen had a RR of 1.86 (95% CI: 1.77–1.96), whereas those who tested false‐positive at third screening had a RR of 2.42 (95% CI: 2.21–2.64). The RR of breast cancer at the screening test after the false‐positive result was 3.95 (95% CI: 3.71–4.21), whereas it decreased to 1.25 (95% CI: 1.17–1.34) three or more screens after the false‐positive result. Women with false‐positive results had a twofold risk of screen‐detected breast cancer compared to women with negative tests. The risk remained significantly higher three or more screens after the false‐positive result. The increased risk should be considered when discussing stratified screening strategies.

Trends in Detection of Invasive Cancer and Ductal Carcinoma In Situ at Biennial Screening Mammography in Spain: A Retrospective Cohort Study

Background Breast cancer incidence has decreased in the last decade, while the incidence of ductal carcinoma in situ (DCIS) has increased substantially in the western world. The phenomenon has been attributed to the widespread adaption of screening mammography. The aim of the study was to evaluate the temporal trends in the rates of screen detected invasive cancers and DCIS, and to compare the observed trends with respect to hormone replacement therapy (HRT) use along the same study period. Methods Retrospective cohort study of 1,564,080 women aged 45–69 years who underwent 4,705,681 screening mammograms from 1992 to 2006. Age-adjusted rates of screen detected invasive cancer, DCIS, and HRT use were calculated for first and subsequent screenings. Poisson regression was used to evaluate the existence of a change-point in trend, and to estimate the adjusted trends in screen detected invasive breast cancer and DCIS over the study period. Results The rates of screen detected invasive cancer per 100.000 screened women were 394.0 at first screening, and 229.9 at subsequent screen. The rates of screen detected DCIS per 100.000 screened women were 66.8 at first screen and 43.9 at subsequent screens. No evidence of a change point in trend in the rates of DCIS and invasive cancers over the study period were found. Screen detected DCIS increased at a steady 2.5% per year (95% CI: 1.3; 3.8), while invasive cancers were stable. Conclusion Despite the observed decrease in breast cancer incidence in the population, the rates of screen detected invasive cancer remained stable during the study period. The proportion of DCIS among screen detected breast malignancies increased from 13% to 17% throughout the study period. The rates of screen detected invasive cancer and DCIS were independent of the decreasing trend in HRT use observed among screened women after 2002.

The cumulative risk of false-positive results in the Norwegian Breast Cancer Screening Program: updated results.

Some false‐positive results are inevitable in mammographic screening, but the impact of false‐positive findings on the program and the participants is a disadvantage of screening. The objective of the current study was to estimate the cumulative risk of a false‐positive result over 10 biennial screening examinations and the cumulative risk of undergoing an invasive procedure with a benign outcome in women screened between the ages of 50 years to 69 years.

Risk of Breast Cancer in Women with False-Positive Results according to Mammographic Features

Purpose To assess the risk of breast cancer in women with false-positive screening results according to radiologic classification of mammographic features. Materials and Methods Review board approval was obtained, with waiver of informed consent. This retrospective cohort study included 521 200 women aged 50-69 years who underwent screening as part of the Spanish Breast Cancer Screening Program between 1994 and 2010 and who were observed until December 2012. Cox proportional hazards regression analysis was used to estimate the age-adjusted hazard ratio (HR) of breast cancer and the 95% confidence interval (CI) in women with false-positive mammograms as compared with women with negative mammograms. Separate models were adjusted for screen-detected and interval cancers and for screen-film and digital mammography. Time without a breast cancer diagnosis was plotted by using Kaplan-Meier curves. Results When compared with women with negative mammograms, the age-adjusted HR of cancer in women with false-positive results was 1.84 (95% CI: 1.73, 1.95; P < .001). The risk was higher in women who had calcifications, whether they were (HR, 2.73; 95% CI: 2.28, 3.28; P < .001) or were not (HR, 2.24; 95% CI: 2.02, 2.48; P < .001) associated with masses. Women in whom mammographic features showed changes in subsequent false-positive results were those who had the highest risk (HR, 9.13; 95% CI: 8.28, 10.07; P < .001). Conclusion Women with false-positive results had an increased risk of breast cancer, particularly women who had calcifications at mammography. Women who had more than one examination with false-positive findings and in whom the mammographic features changed over time had a highly increased risk of breast cancer. Previous mammographic features might yield useful information for further risk-prediction models and personalized follow-up screening protocols. (©) RSNA, 2016 Online supplemental material is available for this article.

Mode of detection: an independent prognostic factor for women with breast cancer.

Objectives To investigate breast cancer survival and risk of breast cancer death by detection mode (screen-detected, interval, and detected outside the screening programme), adjusting for prognostic and predictive tumour characteristics. Methods Information about detection mode, prognostic (age, tumour size, histologic grade, lymph node status) and predictive factors (molecular subtypes based on immunohistochemical analyses of hormone receptor status (estrogen and progesterone) and Her2 status) were available for 8344 women in Norway aged 50–69 at diagnosis of breast cancer, 2005–2011. A total of 255 breast cancer deaths were registered by the end of 2011. Kaplan-Meier method was used to estimate six years breast cancer specific survival and Cox proportional hazard model to estimate hazard ratio (HR) for breast cancer death by detection mode, adjusting for prognostic and predictive factors. Results Women with screen-detected cancer had favourable prognostic and predictive tumour characteristics compared with interval cancers and those detected outside the screening programme. The favourable characteristics were present for screen-detected cancers, also within the subtypes. Adjusted HR of dying from breast cancer was two times higher for women with symptomatic breast cancer (interval or outside the screening), using screen-detected tumours as the reference. Conclusions Detection mode is an independent prognostic factor for women diagnosed with breast cancer. Information on detection mode might be relevant for patient management to avoid overtreatment.

Positive predictive values by mammographic density and screening mode in the Norwegian Breast Cancer Screening Program

OBJECTIVE To investigate the probability of breast cancer among women recalled due to abnormal findings on the screening mammograms (PPV-1) and among women who underwent an invasive procedure (PPV-2) by mammographic density (MD), screening mode and age. METHODS We used information about 28,826 recall examinations from 26,951 subsequently screened women in the Norwegian Breast Cancer Screening Program, 1996-2010. The radiologists who performed the recall examinations subjectively classified MD on the mammograms into three categories: fatty (<30% fibroglandular tissue); medium dense (30-70%) and dense (>70%). Screening mode was defined as screen-film mammography (SFM) and full-field digital mammography (FFDM). We examined trends of PPVs by MD, screening mode and age. We used logistic regression to estimate odds ratio (OR) of screen-detected breast cancer associated with MD among women recalled, adjusting for screening mode and age. RESULTS PPV-1 and PPV-2 decreased by increasing MD, regardless of screening mode (p for trend <0.05 for both PPVs). PPV-1 and PPV-2 were statistically significantly higher for FFDM compared with SFM for women with fatty breasts. Among women recalled, the adjusted OR of breast cancer decreased with increasing MD. Compared with women with fatty breasts, the OR was 0.90 (95% CI: 0.84-0.96) for those with medium dense breasts and 0.85 (95% CI: 0.76-0.95) for those with dense breasts. CONCLUSION PPVs decreased by increasing MD. Fewer women needed to be recalled or undergo an invasive procedure to detect one breast cancer among those with fatty versus dense breasts in the screening program in Norway, 1996-2010.

Association between socioeconomic deprivation and colorectal cancer screening outcomes: Low uptake rates among the most and least deprived people

Background Screening with faecal occult blood tests reduces colorectal cancer-related mortality; however, age, sex and socioeconomic factors affect screening outcomes and could lead to unequal mortality benefits. The aim of this study was to describe the main outcomes of the population-based Barcelona colorectal cancer screening programme (BCRCSP) by deprivation. Methods Retrospective study of the eligible population of the first round of the BCRCSP. Participants’ postal addresses were linked with the MEDEA database to obtain the deprivation quintiles (Dq). Chi-squared tests were used to compare proportions across variables and logistic regression was used to estimate the adjusted effects of age, sex and deprivation on uptake, FIT positivity, colonoscopy adherence and advanced neoplasia detection rate. Results Overall uptake was 44.7%, higher in Dq2, 3 and 4 (OR 1.251, 1.250 and 1.276, respectively) than in the least deprived quintile (Dq 1), and lowest in Dq5 (OR 0.84). Faecal immunochemical test (FIT) positivity and the percentage of people with detectable faecal haemoglobin below the positivity threshold increased with deprivation. The advanced neoplasia detection rate was highest in Dq4. Conclusion Unlike most regions where inequalities are graded along the socioeconomic continuum, inequalities in the uptake of colorectal cancer screening in Spain seem to be concentrated first in the most disadvantaged group and second in the least deprived group. The correlation of deprivation with FIT-positivity and faecal haemoglobin below the positivity threshold is worrying due to its association with colorectal cancer and overall mortality.

Mammographic density and histopathologic characteristics of screen-detected tumors in the Norwegian Breast Cancer Screening Program

Background High mammographic density might mask breast tumors, resulting in delayed diagnosis or missed cancers. Purpose To investigate the association between mammographic density and histopathologic tumor characteristics (histologic type, size, grade, and lymph node status) among women screened in the Norwegian Breast Cancer Screening Program. Material and Methods Information about 1760 screen-detected ductal carcinoma in situ (DCIS) and 7366 invasive breast cancers diagnosed among women aged 50–69 years, 1996–2010, was analyzed. The screening mammograms were classified subjectively according to the amount of fibroglandular tissue into fatty, medium dense, and dense by breast radiologists. Chi-square test was used to compare the distribution of tumor characteristics by mammographic density. Odds ratio (OR) of tumor characteristics by density was estimated by means of logistic regression, adjusting for screening mode (screen-film and full-field digital mammography), and age. Results Mean and median tumor size of invasive breast cancers was 13.8 and 12 mm, respectively, for women with fatty breasts, and 16.2 and 14 mm for those with dense breasts. Lymph node positive tumors were identified among 20.6% of women with fatty breasts compared with 27.2% of those with dense breasts (P < 0.001). The proportion of DCIS was significantly lower for women with fatty (15.8%) compared with dense breasts (22.0%). Women with dense breasts had an increased risk of large (OR, 1.44; 95% CI, 1.18–1.73) and lymph node positive tumors (OR, 1.26; 95% CI, 1.05–1.51) compared with women with fatty and medium dense breasts. Conclusion High mammographic density was positively associated with tumor size and lymph node positive tumors.