Risk Factors and Tumor Characteristics of Interval Cancers by Mammographic Density

Purpose To compare tumor characteristics and risk factors of interval breast cancers and screen-detected breast cancers, taking mammographic density into account. Patients and Methods Women diagnosed with invasive breast cancer from 2001 to 2008 in Stockholm, Sweden, with data on tumor characteristics (n = 4,091), risk factors, and mammographic density (n = 1,957) were included. Logistic regression was used to compare interval breast cancers with screen-detected breast cancers, overall and by highest and lowest quartiles of percent mammographic density. Results Compared with screen-detected breast cancers, interval breast cancers in nondense breasts (≤ 20% mammographic density) were significantly more likely to exhibit lymph node involvement (odds ratio [OR], 3.55; 95% CI, 1.74 to 7.13) and to be estrogen receptor negative (OR, 4.05; 95% CI, 2.24 to 7.25), human epidermal growth factor receptor 2 positive (OR, 5.17; 95% CI, 1.64 to 17.01), progesterone receptor negative (OR, 2.63; 95% CI, 1.58 to 4.38), and triple negative (OR, 5.33; 95% CI, 1.21 to 22.46). In contrast, interval breast cancers in dense breasts (> 40.9% mammographic density) were less aggressive than interval breast cancers in nondense breasts (overall difference, P = .008) and were phenotypically more similar to screen-detected breast cancers. Risk factors differentially associated with interval breast cancer relative to screen-detected breast cancer after adjusting for age and mammographic density were family history of breast cancer (OR, 1.32; 95% CI, 1.02 to 1.70), current use of hormone replacement therapy (HRT; OR, 1.84; 95% CI, 1.38 to 2.44), and body mass index more than 25 kg/m2 (OR, 0.49; 95% CI, 0.29 to 0.82). Conclusion Interval breast cancers in women with low mammographic density have the most aggressive phenotype. The effect of HRT on interval breast cancer risk is not fully explained by mammographic density. Family history is associated with interval breast cancers, possibly indicating disparate genetic background of screen-detected breast cancers and interval breast cancers.

Download Full-text

Predictors of mammographic density among women with a strong family history of breast cancer

BMC Cancer ◽

10.1186/s12885-019-5855-2 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Olivia Moran ◽

Andrea Eisen ◽

Rochelle Demsky ◽

Kristina Blackmore ◽

Julia A. Knight ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Body Weight ◽

Family History ◽

Mammographic Density ◽

Premenopausal Women ◽

Percent Density ◽

Strong Family History ◽

Dense Area ◽

History Of

Abstract Background 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. Methods 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. Results 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 (25.3cm2 vs. 53.1cm2; 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. Conclusions 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.

Download Full-text

Radiological review of prior screening mammograms of screen-detected breast cancer

European Radiology ◽

10.1007/s00330-020-07130-y ◽

2020 ◽

Cited By ~ 1

Author(s):

Tone Hovda ◽

Kaitlyn Tsuruda ◽

Solveig Roth Hoff ◽

Kristine Kleivi Sahlberg ◽

Solveig Hofvind

Keyword(s):

Breast Cancer ◽

Mammographic Density ◽

Breast Imaging ◽

Screening Program ◽

Tumor Characteristics ◽

Breast Cancers ◽

Mammographic Finding ◽

Estrogen Receptor Positivity ◽

Screening Mammograms ◽

Screening And Diagnosis

Abstract Objective To perform a radiological review of mammograms from prior screening and diagnosis of screen-detected breast cancer in BreastScreen Norway, a population-based screening program. Methods We performed a consensus-based informed review of mammograms from prior screening and diagnosis for screen-detected breast cancers. Mammographic density and findings on screening and diagnostic mammograms were classified according to the Breast Imaging-Reporting and Data System®. Cases were classified based on visible findings on prior screening mammograms as true (no findings), missed (obvious findings), minimal signs (minor/non-specific findings), or occult (no findings at diagnosis). Histopathologic tumor characteristics were extracted from the Cancer Registry of Norway. The Bonferroni correction was used to adjust for multiple testing; p < 0.001 was considered statistically significant. Results The study included mammograms for 1225 women with screen-detected breast cancer. Mean age was 62 years ± 5 (SD); 46% (567/1225) were classified as true, 22% (266/1225) as missed, and 32% (392/1225) as minimal signs. No difference in mammographic density was observed between the classification categories. At diagnosis, 59% (336/567) of true and 70% (185/266) of missed cancers were classified as masses (p = 0.004). The percentage of histological grade 3 cancers was higher for true (30% (138/469)) than for missed (14% (33/234)) cancers (p < 0.001). Estrogen receptor positivity was observed in 86% (387/469) of true and 95% (215/234) of missed (p < 0.001) cancers. Conclusions We classified 22% of the screen-detected cancers as missed based on a review of prior screening mammograms with diagnostic images available. One main goal of the study was quality improvement of radiologists’ performance and the program. Visible findings on prior screening mammograms were not necessarily indicative of screening failure. Key Points • After a consensus-based informed review, 46% of screen-detected breast cancers were classified as true, 22% as missed, and 32% as minimal signs. • Less favorable prognostic and predictive tumor characteristics were observed in true screen-detected breast cancer compared with missed. • The most frequent mammographic finding for all classification categories at the time of diagnosis was mass, while the most frequent mammographic finding on prior screening mammograms was a mass for missed cancers and asymmetry for minimal signs.

Download Full-text

Predicting risk of estrogen receptor positive breast cancers in postmenopausal women

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.1507 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 1507-1507

Author(s):

R. T. Chlebowski ◽

G. L. Anderson ◽

D. S. Lane ◽

A. Aragaki ◽

T. Rohan ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Estrogen Receptor ◽

Family History ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Postmenopausal Women ◽

Breast Biopsy ◽

Breast Cancers ◽

Estrogen Receptor Positive

1507 Background: Chemoprevention strategies for estrogen receptor positive (ER+) breast cancers are emerging, especially for postmenopausal women, but require methods of targeting appropriate populations. Our objective was to improve the Breast Cancer Risk Assessment Tool [Gail Model (GM)] for estimating ER+ breast cancer risk. Methods: A prospective cohort involving 161,809 postmenopausal women aged 50–79 years, (93,676 in the observational study (OS) and 68,132 in clinical trials (CT)) at Women’s Health Initiative (WHI) Clinical Centers had comprehensive assessment of lifestyle, medication use and breast cancer risk factors. Breast cancer risk from the GM and other models incorporating additional or fewer risk factors and five year incidence of ER + and ER negative (ER-) invasive breast cancers were determined. Main outcome measures were concordance statistics for models predicting breast cancer risk. Results: Of 148,266 women meeting eligibility criteria, (no prior breast cancer and/or mastectomy), 3,236 developed breast cancer. Chronological age and age at menopause, both GM components, were significantly associated with only ER+ but not ER- breast cancer risk (p<0.05 for heterogeneity test). The GM predicted population-based ER+ cancer risk with reasonable accuracy (concordance statistic 0.60, 95% confidence interval (CI) 0.58 to 0.62) but for ER- cancers, the results were equivalent to chance allocation (concordance statistic 0.49, 95% CI 0.45 to 0.54). For ER+ cancers, no additional risk factors improved the GM prediction. However, a simpler model, developed in the OS and tested in the CT population, including only age, family history, and benign breast biopsy was comparable to GM in ER+ breast cancer prediction (concordance statistics 0.58, 95% CI 0.56 to 0.60). Using this model, all women ≥ 55 years old (or ≥ 60 year old if African American) with either a prior breast biopsy or first degree breast cancer family history had five year breast cancer risk of ≥ 1.8%. Conclusions: In postmenopausal women with comprehensive mammography use, the GM identifies populations at increased risk for ER+ breast cancer but not for ER- cancer. A model with fewer variables provides a simpler alternative for identifying populations appropriate for breast cancer chemoprevention interventions. No significant financial relationships to disclose.

Download Full-text

Discordance between Primary Breast Cancer and Ipsilateral Breast Cancer Tumor Recurrence as a Function of Distance

Journal of Clinical Medicine ◽

10.3390/jcm9124033 ◽

2020 ◽

Vol 9 (12) ◽

pp. 4033

Author(s):

Sebastian M. Jud ◽

Reinhard Hatko ◽

Julius Emons ◽

Bianca Lauterbach ◽

Carolin C. Hack ◽

...

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Primary Tumor ◽

Primary Breast Cancer ◽

Tumor Recurrence ◽

Relative Distance ◽

Tumor Characteristics ◽

Breast Cancers ◽

Ipsilateral Breast ◽

Cancer Tumor

Background: Risk factors for ipsilateral breast cancer tumor recurrence (IBTR) are well established and include grading, nodal status, and receptor status. Little is known about the influence of the local distance between the primary tumor and recurrences on changes in tumor characteristics and prognosis. Methods: In a retrospective setting, we analyzed primary breast cancers and their recurrences. Localizations of primary and recurrent breast cancer were recorded to calculate the relative distance in pixels. Analysis was performed regarding tumor characteristics, relative distance between both, and their impact on breast cancer prognosis. Results: In a cohort of 142 patients with ipsilateral recurrence, no statistically significant difference could be shown in the change in tumor characteristics depending on distance. Progesterone receptor (PR) and estrogene receptor (ER) status changed in 22.7% and 14.9% of cases, respectively. human epidermal growth factor receptor 2 (ERBB2, HER2) status changed in 18.3% of cases. Survival was in accordance with the literature, with luminal-A-like tumors as best and triple negative breast cancers (TNBC) as worst prognosis. With a threshold of 162 pixels, the survival was significantly better in the group with shorter distance. Conclusion: Change in tumor characteristics from primary breast cancer to recurrence occurs more often in PR than ER. In contrast to other work, in this dataset, recurrences with a larger distance to the primary tumor had a worse prognosis in univariate analysis. A Cox model might indicate the possibility that this influence is independent of other risk factors.

Download Full-text

Tumor characteristics and family history in relation to mammographic density and breast cancer: The French E3N cohort

Cancer Epidemiology ◽

10.1016/j.canep.2017.07.003 ◽

2017 ◽

Vol 49 ◽

pp. 156-160 ◽

Cited By ~ 7

Author(s):

Gertraud Maskarinec ◽

Laureen Dartois ◽

Suzette Delaloge ◽

John Hopper ◽

Françoise Clavel-Chapelon ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

Mammographic Density ◽

Tumor Characteristics

Download Full-text

Difference in Risk Factors for Breast Cancer by ER Status in an Indigenous African Population

ISRN Oncology ◽

10.1155/2013/463594 ◽

2013 ◽

Vol 2013 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

M. Galukande ◽

H. Wabinga ◽

F. Mirembe ◽

C. Karamagi ◽

A. Asea

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Contraceptive Use ◽

Growth Factor Receptor ◽

Gene Profiling ◽

Sub Saharan Africa ◽

Breast Cancers ◽

Ethical Approval ◽

Sub Saharan ◽

Er Status

Introduction. Breast cancer is the commonest cancer among women globally. In Uganda, it is on the rise, projected at a 4.5% annual ASR increase (age standardized incidence rate). The reasons for this steep increase are not fully established. In the recent past, gene profiling in tumor tissues suggests that breast cancers are divided into subtypes dependent on the presence or absence of oestrogen receptor, progesterone, and human epidermal growth factor receptor 2 (HER 2). These subtypes do have distinctive clinical outcomes and perhaps risk factors from past studies. There is paucity of data on hormonal receptor status and the traditionally known risk factors in sub-Saharan Africa. The purpose of this study therefore was to establish the differences between ER status and the traditionally known risk factors for breast cancer in Uganda. Methods. An observational analytical hospital, based study, carried out at Makerere University, College of Health Sciences. Formalin fixed and paraffin imbedded sections were prepared for haemotoxylin and eosin (H&E) stains and immunohistochemistry (IHC). Ethical approval was obtained. Results. A total of 113 women were recruited. Mean age was 45 years (SD14). There were no significant differences in selected risk factors (setting, age, contraceptive use, parity, breast feeding, or menarche) by ER status although ER negative tumors had significantly higher grade tumors (by a factor of two) compared to ER positive tumors. Conclusion. There were no significant differences among risk factors by ER status contrary to what several other studies suggest. The manifestation of breast cancer in Africa warrants further extensive inquiry.

Download Full-text

Mammographic Density and Risk of Breast Cancer

American Society of Clinical Oncology Educational Book ◽

10.14694/edbook_am.2013.33.e57 ◽

2013 ◽

pp. e57-e62 ◽

Cited By ~ 2

Author(s):

Norman F. Boyd

Keyword(s):

Breast Cancer ◽

Relative Risk ◽

Family History ◽

Hormone Therapy ◽

Mammographic Density ◽

Surrogate Marker ◽

Breast Cancers ◽

Radiographic Appearance ◽

Breast Image ◽

History Of

The radiographic appearance of the breast on mammography varies among women, and reflects variations in breast tissue composition and the different X-ray attenuation characteristics of these tissues. Fat is radiologically lucent and appears dark on a mammogram. Connective and epithelial tissues are radiologically dense and appear light. These variations in appearance are commonly described as the percentage of the breast image that is radiologically dense, or as percent mammographic density (PMD). There is now extensive evidence that PMD is a risk factor for breast cancer, with a 4- to 6-fold gradient in risk between women with 75% or more PMD compared with those with 10% or less. However, the accuracy of risk prediction in individual women is modest. The extent of PMD is associated inversely with greater age, parity, and weight, and is reduced by the menopause and by tamoxifen. PMD is positively associated with greater height, a family history of breast cancer, and is increased by combined hormone therapy. The relative risk associated with density is substantially larger than the relative risk of breast cancer associated with a family history of the disease or any of the menstrual and reproductive risk factors. It is estimated that the risks of breast cancer attributable to density of 50% or more may be 16% for all breast cancers. Although combined hormone therapy and tamoxifen respectively increase a decrease both PMD and breast cancer risk, there is as yet insufficient evidence to use PMD as a surrogate marker for breast cancer.

Download Full-text

Evaluation of known risk factors for breast cancer in Venezuelan patients with breast cancer, benign breast diseases, and without breast pathology

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.1531 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 1531-1531

Author(s):

D. E. Hernandez ◽

A. E. Hernandez ◽

G. C. Garcia

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Family History ◽

Hormone Replacement ◽

Previous History ◽

Breast Diseases ◽

Breast Pathology ◽

Benign Breast Diseases ◽

Ovary Cancer ◽

History Of

1531 Background: Breast cancer (BC) represents the second cause of death from cancer in Venezuelan women, therefore, it is important to study the known risk factors for developing BC in Venezuelan patients. Also, little is known about the importance of these risk factors in patients with benign breast diseases (BBD). Due to this we carried out a prospective case-control study of known risk factors for developing BC in a group of female patients with BC and BBD with the purpose of defining clinical criteria which can be used to orient physicians and patients about the conducts to be followed not only by the patients, but also by their family group. Methods: We included 515 patients with BC, 507 with BBD, and 505 without breast pathology.The following risk factors were identified through a personal interview with each patient: family history of breast and ovary cancer, exposure to female hormones (exogenous and endogenous), and previous history of BBD. Results: The significant results when comparing the BC group with the BBD group were the following: strong family history of BC (p = 0.004), ingestion of oral contraceptives (p = 0.035), lactation (p = 0.00013), hormone replacement therapy (p = 0.000001), and previous history of BBD (p = 0.0000032). The significant results when comparing the BC group with the group without breast pathology were the following: family history of BC (p = 0.0000001), family history of ovary cancer (p = 0.0000001), nulliparity (p = 0.00009), age of first terminal pregnancy (p = 0.000001), number of abortion (p = 0.024), lactation (p = 0.03), and previous history of BBD (p = 0.0000001). A logistic regression model showed that the variables with the highest impact were lactation (p = 0.0001), family history of breast cancer (p = 0.0001), and family history of ovary cancer (p = 0.0001). Conclusions: Even though several hormonal factors were important, lactation and family history of breast and ovary cancer were the most important risk factors. No significant financial relationships to disclose.

Download Full-text

Estrogens and Progestogens in Triple Negative Breast Cancer: Do They Harm?

Cancers ◽

10.3390/cancers13112506 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2506

Author(s):

Mark van Barele ◽

Bernadette A. M. Heemskerk-Gerritsen ◽

Yvonne V. Louwers ◽

Mijntje B. Vastbinder ◽

John W. M. Martens ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Hormone Replacement ◽

Breast Cancers ◽

Younger Women ◽

Alternative Pathways ◽

Increased Risk ◽

History Of ◽

Hormone Sensitive

Triple-negative breast cancers (TNBC) occur more frequently in younger women and do not express estrogen receptor (ER) nor progesterone receptor (PR), and are therefore often considered hormone-insensitive. Treatment of premenopausal TNBC patients almost always includes chemotherapy, which may lead to premature ovarian insufficiency (POI) and can severely impact quality of life. Hormone replacement therapy (HRT) is contraindicated for patients with a history of hormone-sensitive breast cancer, but the data on safety for TNBC patients is inconclusive, with a few randomized trials showing increased risk-ratios with wide confidence intervals for recurrence after HRT. Here, we review the literature on alternative pathways from the classical ER/PR. We find that for both estrogens and progestogens, potential alternatives exist for exerting their effects on TNBC, ranging from receptor conversion, to alternative receptors capable of binding estrogens, as well as paracrine pathways, such as RANK/RANKL, which can cause progestogens to indirectly stimulate growth and metastasis of TNBC. Finally, HRT may also influence other hormones, such as androgens, and their effects on TNBCs expressing androgen receptors (AR). Concluding, the assumption that TNBC is completely hormone-insensitive is incorrect. However, the direction of the effects of the alternative pathways is not always clear, and will need to be investigated further.

Download Full-text