Multivariate model to identify women at low risk of cancer upgrade after a core needle biopsy diagnosis of atypical ductal hyperplasia

Purpose

The aim was to evaluate the role of tumor-infiltrating lymphocytes (TIL) in predicting molecular response after preoperative endocrine or cytotoxic treatment for HR+/HER2? patients who do not achieve a pathological complete response.

Methods

Stromal (Str) TIL were centrally evaluated on samples from diagnostic core-biopsies of HR+/HER2? patients included in two prospective randomized trials: the LETLOB trial (neoadjuvant endocrine-based treatment) and the GIOB trial (neoadjuvant chemotherapy-based treatment). Pre- and post-treatment Ki67 was centrally assessed.

Results

StrTIL were evaluable in 111 cases (n = 73 from the LETLOB trial and n = 38 from the GIOB trial). Median StrTIL was 2%. Patients with high StrTIL (StrTIL ≥10%, n = 28) had more frequently breast cancer of ductal histology (p = 0.02), high grade (p = 0.049), and high Ki67 (p = 0.02). After neoadjuvant endocrine treatment (LETLOB cohort), a significant Ki67 suppression (p < 0.01) from pre- to post-treatment was observed in both the low and high StrTIL groups. High StrTIL patients achieve more frequently a relative Ki67 suppression ≥50% from baseline as compared to low StrTIL patients (55 vs. 35%, p non significant). After neoadjuvant chemotherapy (GIOB cohort), a significant Ki67 suppression was observed only for low StrTIL patients (Wilcoxon p = 0.001) and not in the high StrTIL group (p = 0.612). In this cohort, the rate of patients achieving a relative Ki67 suppression ≥50% from baseline was significantly higher in the high vs low StrTIL group (64 vs. 10%, p = 0.003). Geometric mean Ki67 suppression was evaluated in each cohort according to StrTIL: the lowest value (?41%) was observed for high StrTIL cases treated with chemotherapy.

Conclusions

This hypothesis-generating study suggests that in HR+/HER2? breast cancer StrTIL at baseline may influence the achievement of a molecular response after neoadjuvant treatment. Further evaluation in large studies is needed, and interaction with the type of treatment warrants to be explored.

     

Factors predictive of breast cancer in open biopsy in cases with atypical ductal hyperplasia diagnosed by ultrasound-guided core needle biopsy

Aims

The purpose of the study was to explore factors predictive of breast cancer as diagnosed by excision biopsy in cases with a diagnosis of atypical ductal hyperplasia (ADH) on ultrasound-guided core needle biopsy (CNB).

Patients and methods

We carried out diagnosis of breast lesions by ultrasound-guided CNB in a single hospital in Taiwan from November 2003 to October 2009. Patients who were diagnosed with ADH and subsequently underwent excision biopsy were included in this study (n = 124).

Results

Fifty-six of the 124 patients who were included (45.2%) had cancer, and the remaining 68 had benign lesions. By multivariate analysis of all clinical characteristics and on the basis of the imaging features in these cases, older patient age (≥50 y/o, OR: 3.910, p = 0.005), larger tumour size (≥15 mm, OR: 3.398, p = 0.013), and the presence of architectural distortion by mammography (OR: 10.7, p = 0.036) were found likely to be associated with breast cancer.

Conclusions

Open biopsy is necessary in patients who were diagnosed with ADH on CNB. Older patients (≥50 y/o), with a larger tumour size (≥15 mm) and an abnormal mammography are especially likely to have breast cancer.     

Breast cancer: histological prognosis from biopsy material

Two histological factors to be taken into consideration for prognosis in pretreatment schedules of breast cancer have been studied on a group of 352 cases treated by non-mutilating therapeutics at the Fondation Curie between 1960 and 1970. The tumour material the slides of which we have reexamined "blindly", i.e. ignoring the evolution of the case had been obtained mostly by drill-biopsy. Histological groups and types have been determined following an analytical classification for computer purpose. The degree of malignancy was calculated with the method of Scarff-Bloom-Richardson. The analyzed data have been memorized on computer and then confronted with the elements of the T.N.M. classification and the survival of the patients involved. It appeared that if drill-biopsie have been performed correctly the histological type may be defined in eighty percent of cases. And it is likewise possible to calculate the histological grade of malignancy for each mammary cancer. With such a material the value for prognosis by means of the Scarff-Bloom-Richardson method still remains if applied only to adenocarcinoma of the "common infiltrating type".     

Breast cancer risk management

Breast cancer is a devastating illness that affects tens of thousands of American women each year. Although no one can predict who will actually develop breast cancer, a number of risk factors have been found that allow clinicians to identify the women at highest risk. Recent research has focused on exploring options, such as chemoprevention, to prevent high-risk women from developing breast cancer. The selective estrogen receptor (ER) modulators (SERMs) were a logical choice for chemoprevention because of their well-known estrogen antagonist effects in the breast. Tamoxifen is the best studied of these agents and has been shown to reduce the incidence of all breast cancers by 38% and ER-positive tumors by 48%.(1) However, despite this large potential risk reduction, risk management with chemopreventive agents is still not routine. The primary deterrents are believed to be the significant adverse events associated with tamoxifen as well as a perceived decline in quality of life (QOL).(2-4) These concerns led researchers to consider other possible agents that would still be effective but would have fewer or more acceptable side effects than tamoxifen. Raloxifene was proposed as an alternative to tamoxifen based on its estrogen antagonist effects in the breast and its relative safety as an osteoporosis agent. In this article, we will review the trials that led to the emergence of both tamoxifen and raloxifene as chemopreventive agents and will then offer a management strategy for breast cancer prevention in the primary care setting.     

Atypical hyperplasia and breast cancer risk: a critique

The purpose of this paper is to examine critically the evidence that atypical hyperplasia (AH) is a risk factor for breast cancer. First, we appraised studies that have examined the association between AH and breast cancer risk for their adherence to widely accepted standards for the conduct of research. Second, we examined the a vailable evidence to determine the plausibility of an association between AH and breast cancer risk using the guidelines proposed by Bradford Hill. A total of 18 studies (11 cohort studies, two case-control studies, and five cross-sectional studies) were found that were published in the English language from January 1960 to March 1992 that examined the association of AH as a distinct entity and breast cancer risk. A systematic approach was adopted to examine the collected studies for their adherence to methodologic standards, which showed wide variation among studies. A meta-analysis was carried out, based on a total sample size of 182,980 women. Of 16 studies that gave point estimates of risk, 14 exceeded unity and 12 were significantly different from unity. The pooled estimate from all studies of the association between AH and breast cancer, gave an overall odds ratio (OR) of 3.67 (95 percent confidence interval = 3.16–4.26). The test of the hypothesis of homogeneous association was rejected (² = 151.6, df = 14, P<0.0001), indicating significant variability among the ORs of individual studies. The conclusions from the application of the Bradford Hill criteria indicated strongly that AH is a risk factor for breast cancer.     

Breast cancer recurrence risk in relation to antidepressant use after diagnosis

Background Dietary fats and other constituents have been studied extensively in relation to breast cancer risk. Iron, an essential micronutrient with pro-oxidant properties, has received little attention, and specific fats may augment its toxicity. We investigated the effects of iron and fats from various food sources on the risk of breast cancer. Methods Participants in a population-based case–control study, 3,452 breast cancer cases, and 3,474 age-frequency-matched controls, completed in-person interviews, including a detailed food-frequency questionnaire. Plant- and animal-derived iron and fat intakes were derived from dietary intake data and food composition tables. Unconditional logistic regression models were used to study the independent and interactive effects of different forms of iron and fats on breast cancer risk. Results Animal-derived (largely heme) iron intake was positively associated with breast cancer risk (P _trend < 0.01; OR = 1.49 in the highest vs. lowest quartile, 95% confidence interval [CI] 1.25–1.78) after adjustment for known risk factors, antioxidant vitamin and isoflavone intake, and vitamin supplement use. The effect of animal-derived iron was similar in pre- and postmenopausal women. Intake of animal-derived fats was also associated with increased risk (adjusted OR = 1.34, 95% CI 1.14–1.58), particularly after menopause. A significant interaction between iron and fat from animal sources was observed (P < 0.01). Conclusions A high intake of animal-derived (heme) iron may be associated with an increased risk of primary breast cancer in Chinese women, and saturated and mono-unsaturated fats that are also derived from animal sources may augment this effect. Combined reductions in animal-derived iron and fat consumption have the potential to reduce breast cancer risk.     

Histo-molecular oncogenesis of pancreatic cancer: From precancerous lesions to invasive ductal adenocarcinoma

Pancreatic cancer is a lethal malignancy, whose precursor lesions are pancreatic intraepithelial neoplasm, intraductal papillary mucinous neoplasm, intraductal tubulopapillary neoplasm, and mucinous cystic neoplasm. To better understand the biology of pancreatic cancer, it is fundamental to know its precursors and to study the mechanisms of carcinogenesis. Each of these precursors displays peculiar histological features, as well as specific molecular alterations. Starting from such pre-invasive lesions, this review aims at summarizing the most important aspects of carcinogenesis of pancreatic cancer, with a specific focus on the recent advances and the future perspectives of the research on this lethal tumor type.     

Breast cancer risk: weaving facts into fabric

Breast Cancer Research and Treatment -     

Breast cancer risk factors: PCB congeners.

The chronic effects of polychlorinated biphenyls (PCBs) are a public health concern, and a potential relationship with breast cancer has been postulated. The purpose of this study was to examine the possible relationship between PCBs and breast cancer. All women (134) treated by excision biopsy because of breast lump at Reina Sofia University Hospital, Cordoba, Spain over a period of 10 months were included in our study. They were all administered a questionnaire by interview, calculation of body mass index, histopathological examination of excised mass and chemical estimation of PCB congener levels in breast fat. The collected samples were from 65 (48.5%) women with benign lesions and 69 (51.5%) with malignant lesions. The variables associated with malignant lesions on univariate analysis were age, lactation period, overweight, PCB n-28 and PCB n-52. On the multivariate analysis PCB n-28 was found to be the most important risk factor (OR 9.6, 95% CI 3.8-24.4). Other risk factors were identified as age, drinking alcohol, low parity and overweight. If these findings can be confirmed in a large study population, however, they may have important implications for breast cancer risk.     

Breast cancer: further metabolic-endocrine risk markers?

There is evidence that increased oestrogen receptor (ER) expression in normal mammary epithelium may be a risk marker for the development of breast cancer. Insulin-like growth factor 1 (IGF1) is a potent inducer of mitosis and has been shown to synergize with oestrogen in stimulating the growth of human breast cancer in vitro. In these cells oestradiol has been shown to upregulate IGF type 1 receptor (IGFR), and recently a similar effect has been reported in normal human breast tissue xenografts in vivo. It has been postulated that the combined effect of oestradiol and IGF1 may stimulate proliferation in normal mammary epithelium and increase breast cancer risk. The bioavailability of IGF1 to the tissues is modulated by IGF-binding proteins (IGFBPs), and higher circulating levels of IGF1 and lower levels of IGFBP3 have been reported in breast cancer patients. Breast cancer specimens show a positive correlation between ER status and IGF receptor status, and also a negative correlation between ER status and IGFBP3 expression. Finally, ectopic growth hormone expression has been shown in a majority of specimens of normal and malignant breast tissue, and this may contribute to breast cancer risk, possibly by increasing the local level of bioavailable IGF1. Expansion of such findings may provide clinically useful markers of increased risk to breast cancer in women.     

Breast lesions in reduction mammaplasty specimens: a histopathological pattern in 534 patients

Background:

The prevalence of breast lesions (benign, precancerous and cancer lesions) in reduction mammaplasty (RM) specimens has rarely been reported in Europe and never in the Swiss population.

Methods:

Personal and histopathological data from 534 female patients who underwent RM were reviewed.

Results:

Benign and/or malignant lesions were detected in 76.2% of all patients. Benign breast lesions associated with an increased risk of developing breast cancer represented 2.8% of all lesions. Breast cancer in situ was identified in 5 (0.9%) patients. Patient age and previous history of breast cancer were risk factors for incidental breast cancer.

Conclusion:

The rate of incidental carcinoma in situ was higher for patients with breast cancer history. Probably due to preoperative breast cancer investigation, no occult invasive breast cancer was found in reduction mammary specimens. Therefore before RM, breast cancer evaluation should be considered for all patients, especially for those with breast cancer risk factors (e.g., patient age, personal history of breast cancer).     

Breast cancer risk: a review of definitions and assessments of risk

The histopathological and biochemical characteristics of cells and multicellular structure of benign and malignant breast changes have highly significant implications as to the risk of acquiring and dying of breast cancer. Consequently, every breast biopsy merits highly specific histopathological characterization as well as assay for hormone receptors. Certain aspects of a woman's personal and family history may be associated with increased or decreased risk. Clinical application of these variables to the prediction of future outcome requires an understanding of the definitions of risk. These definitions must then be applied appropriately when assessing risk. The definition of risk used must be explicitly stated and consistently used. Provided is a review of the definitions of risk and the risk of acquiring breast cancer according to age, family history, and histopathological characteristics of benign breast biopsies. The highly variable relative risk of dying from breast cancer when diagnosed is also reviewed.