Progression risk of columnar cell lesions of the breast diagnosed in core needle biopsies

Columnar cell lesions (CCLs) of the breast are recognized as putative precursor lesions of invasive carcinoma, but their management remains controversial. We therefore conducted a retrospective study on 311 CCLs, diagnosed in 4,164 14-gauge core needle biopsies (CNB): 221 CCLs without atypia (CCL), 69 with atypia (CCL-A), and 21 atypical ductal hyperplasias originating in CCL (ADH-CCL). Two groups were identified: "immediate treatment" group undergoing excision within four months after the CNB diagnosis of CCL (N = 52) and the "wait-and-see" group followed up to 8 years (median 3.5 years, N = 259). In 7 of 31 women (22.5%, 1 CCL, 4 CCL-A, 2 ADH-CCL) who underwent immediate surgical excision and were initially biopsied for microcalcifications, ductal carcinoma in situ (DCIS) was present and in 2/31 women (6.5%, 1 CCL, 1 CCL-A) invasive carcinoma. In 2/21 excisions (9.5%, 1 CCL, 1 CCL-A) initially biopsied for a density, DCIS was present and invasive carcinoma in 5/21 excisions (23.8%, 2 CCL, 3 CCL-A). In the wait-and-see group, 9/259 women (3.5%) developed invasive carcinoma, 6 ipsi, and 3 contralaterally. Progression risks of CCL-A and ADH-CCL were 18% and 22%,versus 2% for CCL without atypia (p < 0.001). In conclusion, CCL-A or ADH-CCL in a CNB were associated with a high risk of DCIS/invasive carcinoma in immediate surgical excision biopsies. The 8-years progression risks for CCL-A and ADH-CCL were around 20%. This illustrates that an atypical CCL in a CNB may signal the presence of concurrent lesions or development of advanced lesions in future and may justify ("mini") surgical excision.     

Clinicopathologic characteristics of carcinomas that develop after a biopsy containing columnar cell lesions: evidence against a precursor role

BACKGROUND:

Columnar cell lesions are frequently associated with atypical ductal hyperplasia, lobular neoplasia, and tubular carcinoma, and have been suggested as a precursor lesion for low‐grade carcinomas. However, in long‐term follow‐up studies, columnar cell lesions are associated with only a slight increase in later breast cancer development. If columnar cell lesions are precursor lesions, one would expect subsequent cancers to develop at the same site as the biopsy and to be preferentially of low grade. The goal of this article is to review the clinical and pathologic features of carcinomas that develop after a diagnosis of columnar cell lesion to try to establish whether these lesions are precursors to low‐grade invasive carcinoma.

METHODS:

The authors reviewed biopsies containing columnar cell lesions, using the criteria of Schnitt and Vincent‐Salomon, from 77 women in the Nashville Breast Cohort who developed subsequent breast carcinoma. Clinicopathologic features including laterality, type, and grade of the subsequent cancer were recorded.

RESULTS:

Breast cancer developed a median of 11 years after initial biopsy. The median age at diagnosis was 60 years. The majority of invasive carcinomas were of no special type and of intermediate grade. Moreover, the carcinomas were as likely to occur in the contralateral breast as in the breast that was originally diagnosed with columnar cell lesion, regardless of columnar cell lesion subtype (P = .48).

CONCLUSIONS:

Carcinoma subsequent to columnar cell lesions may occur in either breast and tends to show a similar grade and type distribution as sporadic breast cancer. These findings argue against columnar cell lesions being a true precursor for low‐grade invasive carcinoma. Cancer 2012. © 2011 American Cancer Society.     

Columnar cell lesions and subsequent breast cancer risk: a nested case-control study

Introduction  

Histologic and genetic evidence suggests that at least some columnar cell lesions (CCL) of the breast represent precursor lesions in the low-grade breast neoplasia pathway. However, the risk of subsequent breast cancer associated with the presence of CCL in a benign breast biopsy is poorly understood.     

Diabetes mellitus and breast cancer: a retrospective population-based cohort study

SummaryPurpose Evidence suggests that women with type 2 diabetes may be at increased risk of breast cancer, possibly due to chronic exposure to insulin resistance and/or hyperinsulinemia. The purpose of this study was to compare the incidence of breast cancer in postmenopausal women with and without diabetes.Methods Using population-based validated health databases from Ontario, Canada, this retrospective cohort study compared breast cancer incidence between women, aged 55–79 years, with newly diagnosed diabetes (n=73,796) to women without diabetes (n=391,714).Results Women with diabetes were slightly older, were more likely to reside in a lower income neighborhood, had greater comorbidity, and had more annual physician visits than women without diabetes. After 2.2 million person-years of follow-up from 1994 to 2002, breast cancer incidence was 2.97/1000 person-years in the diabetes group and 2.75/1000 person-years in the non-diabetes group. After adjustment for age and income, there was a significant increase in breast cancer among women with diabetes (hazard ratio, HR, 1.08, 95% confidence interval, CI, 1.01–1.16, p=0.021).Conclusion This study found a small but significant increase in incident breast cancer in a predominantly postmenopausal population of women with diabetes, when compared to women without diabetes. These results support the possibility that insulin resistance or some other aspect of type 2 diabetes may promote breast cancer, and may further direct treatment and prevention strategies.     

Dietary and other risk factors in women having fibrocystic breast conditions with and without concurrent breast cancer: a nested case-control study in Shanghai, China

Risk of breast cancer is increased in women with proliferative benign breast conditions. Most of these conditions, however, do not progress to breast cancer. The purpose of our study was to identify factors possibly associated with this progression. Women with proliferative fibrocystic breast conditions alone (214), and women with proliferative fibrocystic breast conditions and concurrent breast cancer (130), were compared to each other, and each of these groups of women were also compared to 1,070 controls; and 176 women with non-proliferative benign breast conditions alone, and 155 also with breast cancer, were similarly compared. All study subjects were selected from a cohort of women enrolled in a trial of breast self-examination in Shanghai. Women were interviewed to ascertain information on suspected risk factors for breast cancer and dietary habits. Conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Increased risks of both proliferative fibrocystic breast conditions alone, and with breast cancer, were associated with low parity, a prior benign breast lump and breast cancer in a first-degree relative. Decreasing trends in the risk of both conditions with increasing intake of fruits and vegetables were observed. No factors were significantly associated with risk of breast cancer relative to risk of proliferative changes. Similar, but in some instances weaker, associations were observed for non-proliferative fibrocystic conditions with and without breast cancer. The possible risk or protective factors that were observed in our study most likely alter the risk of breast cancer at an early stage in the carcinogenic process, and probably do not alter risk of progression from proliferative fibrocystic breast conditions to breast cancer.     

Columnar cell lesions,mammographic density and breast cancer risk

Background Mammographic density is the third largest risk factor for ductal carcinoma in-situ (DCIS) and invasive breast cancer. However, the question of whether risk-mediating precursor histological changes, such as columnar cell lesions (CCLs), can be found in dense but non-malignant breast tissues has not been systematically addressed. We hypothesized that CCLs may be related to breast composition, in particular breast density, in non-tumour containing breast tissue. Patients and methods We examined randomly selected tissue samples obtained by bilateral subcutaneous mastectomy from a forensic autopsy series, where tissue composition was assessed, and in which there had been no selection of subjects or histological specimens for breast disease. We reviewed H&E slides for the presence of atypical and non-atypical CCLs and correlated with histological features measured using quantitative microscopy. Results CCLs were seen in 40 out of 236 cases (17%). The presence of CCLs was found to be associated with several measures of breast tissue composition, including radiographic density: high Faxitron Wolfe Density (P = 0.037), high density estimated by percentage non-adipose tissue area (P = 0.037), high percentage collagen (P = 9.2E−05) and high percentage glandular area (P = 2E−05). DCIS was identified in two atypical CCL cases. The extent of CCL was not associated with any of the examined variables. Conclusion Our study is the first to report a possible association between CCLs and breast tissue composition, including mammographic density. Our data suggest that prospective elucidation of the strength and nature of the clinicopathological correlation may lead to an enhanced understanding of mammographic density and evidence based management strategies. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Interaction of dense breast patterns with other breast cancer risk factors in a case-control study

The question of interactions between breast density and other breast cancer risk factors is of interest, since it bears upon the use of density as a marker for changes in breast cancer risk. We studied breast parenchymal patterns and 13 other potential risk factors for breast cancer in 172 breast cancer cases and 338 age-matched controls in Singapore. Dense breast patterns were defined as having Tabar parenchymal pattern IV or V. We found significant interactions between dense patterns and ethnic group (P=0.046), and between dense patterns and number of deliveries (P=0.04). Among women with nondense breast patterns, the non-Chinese had lower risk than the Chinese with an odds ratio (OR) of 0.47 (95% CI 0.24, 0.88), whereas in those with dense patterns, the non-Chinese had considerably higher risks (OR=5.34, 95% CI 0.54, 52.51). Alternatively expressed, the increased risk with dense patterns was only observed in the non-Chinese (OR=13.99, 95% CI 1.33, 146.99). Among parous women, the protective effect of three or more deliveries was only observed in those with dense breast patterns (OR=0.21, 95% CI 0.06, 0.70). Suggestive but nonsignificant interactions with dense patterns were observed for ever having delivered, age at first delivery, breast feeding and body mass index. The results are consistent with dense breast patterns as a marker for hormonal modification of breast cancer risk.     

Alcohol consumption and risk of breast cancer: a cohort study

Objectives: To study the association between alcohol consumption and breast cancer risk. Methods: A case–cohort analysis was undertaken within the cohort of 56,837 women who were enrolled in the Canadian National Breast Screening Study (NBSS) and who completed a self-administered dietary questionnaire. (The NBSS is a randomized controlled trial of screening for breast cancer in women aged 40–59 at recruitment.) The cohort was recruited between 1980 and 1985, and during follow-up to the end of 1993 a total of 1469 women in the dietary cohort were diagnosed with biopsy-confirmed incident breast cancer. For comparative purposes a subcohort consisting of a random sample of 5681 women was selected from the full dietary cohort. After exclusions for various reasons the analyses were based on 1336 cases and 5238 noncases. Results: When compared to nondrinkers the adjusted incidence rate ratios (95% confidence intervals) for those consuming>0 and 10g of alcohol/day, >10 and 20g/day, >20 and thinsp;30g/day, >30 and 40g/day, >40 and 50g/day, and >50g/day were 1.01 (0.84–1.22), 1.16 (0.91–1.47), 1.27 (0.91–1.78), 0.77 (0.51–1.16), 1.00 (0.57–1.75), and 1.70 (0.97–2.98), respectively; the associated p value for the test for trend was 0.351. Similar findings were obtained when analyses were conducted separately in the screened and control arms of the NBSS, in premenopausal and postmenopausal women, for screen-detected and interval-detected breast cancer, and by levels of other breast cancer risk factors. Conclusions: The results of this study suggest that alcohol consumption might be associated with increased risk of breast cancer at relatively high levels of intake.     

Serum enterolactone concentration is not associated with breast cancer risk in a nested case-control study

The lignan enterolactone produced by the intestinal microflora from dietary precursors has been hypothesized to protect against hormone-dependent cancers. We conducted a nested case-control study to examine the relationship between serum enterolactone concentration and risk of breast cancer. Enterolactone concentrations were measured by time-resolved fluoroimmunoassay in serum collected at 4 independent cross-sectional population surveys from 206 women with breast cancer diagnosed during follow-up (mean 8.0 years) and from 215 controls frequency-matched to cases by study cohort, 5-year age group and study area. Mean serum enterolactone concentration (nmol/l) did not significantly differ between case and control subjects [25.2 (SD 22.2) vs. 24.0 (SD 21.3), respectively]. Odds ratios for breast cancer risk estimated by conditional logistic regression for increasing concentration of enterolactone in quartiles were 1.00 (referent), 1.67 (95% CI 0.95-2.95), 1.71 (95% CI 0.96-3.06) and 1.30 (95% CI 0.73-2.31), and p for trend was 0.48. Our findings do not support the hypothesis that high serum enterolactone concentration is associated with reduced risk of breast cancer.     

Change of mammographic density predicts the risk of contralateral breast cancer - a case-control study

Introduction

Mammographic density is a strong risk factor for breast cancer, but it is unknown whether density at first breast cancer diagnosis and changes during follow-up influences risk of non-simultaneous contralateral breast cancer (CBC).

Methods

We collected mammograms for CBC-patients (cases, N = 211) and unilateral breast cancer patients (controls, N = 211), individually matched on age and calendar period of first breast cancer diagnosis, type of adjuvant therapy and length of follow-up (mean follow-up time: 8.25 years). The odds of CBC as a function of changes of density during follow-up were investigated using conditional logistic regression, adjusting for non-dense area at diagnosis.

Results

Patients who experienced ≥10% absolute decrease in percent density had a 55% decreased odds of CBC (OR = 0.45 95% CI: 0.24 to 0.84) relative to patients who had little or no change in density from baseline to first follow-up mammogram (mean = 1.6 (SD = 0.6) years after diagnosis), whereas among those who experienced an absolute increase in percent density we could not detect any effect on the odds of CBC (OR = 0.83 95% CI: 0.24 to 2.87).

Conclusion

Decrease of mammographic density within the first two years after first diagnosis is associated with a significantly reduced risk of CBC, this potential new risk predictor can thus contribute to decision-making in follow-up strategies and treatment.     

Dietary and stored iron as predictors of breast cancer risk: A nested case–control study in Shanghai

Increases in risk of breast cancer in successive generations of migrants to the United States from China and rapid temporal changes in incidence rates in China following social and economic changes clearly implicate environmental factors in the etiology of this disease. Case–control and cohort studies have provided evidence that at least some of these factors may be dietary. Iron, an essential element necessary for cell function, has also been demonstrated to have potential carcinogenic and co‐carcinogenic activities. Iron overload, which was previously uncommon, has become more common in the United States than iron deficiency and may be increasing in China concurrently with dramatic increases in meat consumption. A case–control study nested in a cohort of women in Shanghai, China, was conducted to evaluate possible associations between risk of proliferative and nonproliferative fibrocystic changes as well as breast cancer and dietary iron intake and plasma ferritin levels. Plasma ferritin levels and reported dietary iron intake were compared in 346 women with fibrocystic changes, 248 breast cancer cases and 1,040 controls. Increasing ferritin levels were significantly associated with increasing risk of nonproliferative fibrocystic changes (OR: 2.51, 95% CI: 1.16–5.45, p trend = 0.04). Similar, but weaker, trends were observed for proliferative changes and for breast cancer. Risk of breast cancer relative to the risk of fibrocystic changes was associated with dietary iron intake in women with nonproliferative fibrocystic changes (OR: 2.63, 95% CI: 1.04–6.68, p = 0.02). In conclusion, this study finds significant associations between iron (stored and dietary) and fibrocystic disease and breast cancer. © 2009 UICC     

Lactation and breast cancer risk: a case-control study in Connecticut

In this report, we examined the relationship between lactation and breast cancer risk, in a case-control study of breast cancer, conducted in Connecticut between 1994 and 1998. Included were 608 incident breast cancer cases and 609 age frequency matched controls, aged 30-80 years old. Cases and controls were interviewed by trained study interviewers, using a standardized, structured questionnaire, to obtain information on lactation and other major risk factors. Parous women who reported ever lactation had a borderline significantly reduced risk of breast cancer (OR = 0.83, 95% CI, 0.63-1.09). An OR of 0.53 (95% CI, 0.27-1.04) was observed in those having breastfed more than 3 children compared to those who never lactated. Women having breastfed their first child for more than 13 months had an OR of 0.47 (95% CI, 0.23-0.94) compared to those who never breastfed. Lifetime duration of lactation also showed a risk reduction while none of the ORs were statistically significant. Further stratification by menopausal status showed a risk reduction related to lactation for both pre- and postmenopausal women, while the relationship is less consistent for the latter. These results support an inverse association between breastfeeding and breast cancer risk.     

Perfluorinated alkylated substances serum concentration and breast cancer risk: Evidence from a nested case-control study in the French E3N cohort

Endocrine-disrupting chemicals are proposed to increase breast cancer (BC) incidence. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), two perfluorinated alkylated substances (PFASs), are suspected to be ubiquitously present in the blood of human population worldwide. We investigated the associations between serum concentrations of these substances and BC risk. Etude Epidémiologique auprès de femmes de l'Education Nationale is a cohort of 98,995 French women born in 1925–1950 and followed up since 1990. We sampled 194 BC cases and 194 controls from women with available blood samples. Serum concentrations of PFASs were measured by liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS). Adjusted conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two sided. While PFASs concentrations were not associated with BC risk overall, we found positively linear associations between PFOS concentrations and the risk of ER+ (3rd quartile: OR = 2.22 [CI = 1.05–4.69]; 4th quartile: OR = 2.33 [CI = 1.11–4.90]); P_trend = 0.04) and PR+ tumors (3rd quartile: OR = 2.47 [CI = 1.07–5.65]; 4th quartile: OR = 2.76 [CI = 1.21–6.30]; P_trend = 0.02). When considering receptor-negative tumors, only the 2nd quartile of PFOS was associated with risk (ER−: OR = 15.40 [CI = 1.84–129.19]; PR−: OR = 3.47 [CI = 1.29–9.15]). While there was no association between PFOA and receptor-positive BC risk, the 2nd quartile of PFOA was positively associated with the risk of receptor-negative tumors (ER−: OR = 7.73 [CI = 1.46–41.08]; PR−: OR = 3.44 [CI = 1.30–9.10]). PFAS circulating levels were differentially associated with BC risk. While PFOS concentration was linearly associated with receptor-positive tumors, only low concentrations of PFOS and PFOA were associated with receptor-negative tumors. Our findings highlight the importance of considering exposure to PFASs as a potential risk factor for BC.     

Breast cancer risk associated with estrogen receptor expression in epithelial hyperplasia lacking atypia and adjacent lobular units

Estrogen is associated with many epidemiologic risk factors for invasive breast cancer. Cells that express estrogen receptors (ERs) in epithelial hyperplasia lacking atypia (EHLA) may influence breast cancer progression. We conducted a nested case-control study of 268 women with biopsy-confirmed EHLA to determine whether immunohistochemical expression of ERalpha in EHLA affects subsequent breast cancer risk. Study subjects could not have a prior or current history of breast cancer or atypical hyperplasia. Immunohistochemical stains in individual lesions and adjacent normal lobules were considered positive if >or= 10% of epithelial cells stained for ERalpha. The risk of invasive breast cancer in EHLA patients with ERalpha-positive normal lobules was twice that of other EHLA patients (95% CI = 1.0-3.8). This risk was not affected by the ERalpha status of EHLA lesions. ERalpha expression in adjacent normal lobules increases the moderate breast cancer risk previously associated with EHLA.     

Selenium and the risk of postmenopausal breast cancer in the DOM cohort

Summary Selenium has been claimed to have chemo-preventive properties. However, data showing that in humans selenium levels are already decreased prior to diagnosis of breast cancer were not available. Such information is mandatory before oral selenium supplementation in the primary prevention of (breast) cancer in humans is acceptable. This question of a preventive-potential of selenium was evaluated in a case-control study nested in a cohort, because this design allows determination of the time-order of preceding selenium levels and subsequent cancer risk.The cohort consisted of 5577 women aged 55–70 years from the DOM project, a population based breast cancer screening program in the Netherlands. Instrumental Neutron Activation Analysis was used to measure the selenium content of toenail clippings. The 69 cases of breast cancer found during follow-up after screening represent recent tumours since all women had a negative screening mammogram 3–5 years previously.No decreased selenium levels, as measured in nail clippings from the big toes, could be detected in cases-to-be, either when compared to 4 age matched controls per case or when compared with a random control group drawn from the entire cohort. On the contrary, a tendency for slightly higher selenium levels among future cancer cases was observed.As to the sensitivity of detecting differences in selenium by nail clippings, lower selenium could be detected in nails of current smokers. The smoking-related decrease in nail selenium level was of the same order as the differences between breast cancer cases and controls, but was independent of the breast cancer risk.Results are similar to a comparable study on premenopausal breast cancer and argue against a preventive role for selenium on breast cancer risk.