The impact of adjuvant therapy on contralateral breast cancer risk and the prognostic significance of contralateral breast cancer: a population based study in the Netherlands

Background The impact of age and adjuvant therapy on contralateral breast cancer (CBC) risk and prognostic significance of CBC were evaluated. Patients and Methods In 45,229 surgically treated stage I–IIIA patients diagnosed in the Netherlands between 1989 and 2002 CBC risk was quantified using standardised incidence ratios (SIRs), cumulative incidence and Cox regression analysis, adjusted for competing risks. Results Median follow-up was 5.8 years, in which 624 CBC occurred <6 months after the index cancer (synchronous) and 1,477 thereafter (metachronous). Older age and lobular histology were associated with increased synchronous CBC risk. Standardised incidence ratio (SIR) of CBC was 2.5 (95% confidence interval (95% CI) 2.4–2.7). The SIR of metachronous CBC decreased with index cancer age, from 11.4 (95% CI 8.6–14.8) when <35 to 1.5 (95% CI 1.4–1.7) for ≥60 years. The absolute excess risk of metachronous CBC was 26.8/10,000 person-years. The cumulative incidence increased with 0.4% per year, reaching 5.9% after 15 years. Adjuvant hormonal (Hazard rate ratio (HR) 0.58; 95% CI 0.48–0.69) and chemotherapy (HR 0.73; 95% CI 0.60–0.90) were associated with a markedly decreased CBC risk. A metachronous CBC worsened survival (HR 1.44; 95% CI 1.33–1.56). Conclusion Young breast cancer patients experience high synchronous and metachronous CBC risk. Adjuvant hormonal or chemotherapy considerably reduced the risk of CBC. CBC occurrence adversely affects prognosis, emphasizing the necessity of long-term surveillance directed at early CBC-detection

Digital vs screen-film mammography in population-based breast cancer screening:performance indicators and tumour characteristics of screen-detected and interval cancers

Background: Full-field digital mammography (FFDM) has replaced screen-film mammography (SFM) in most breast cancer screening programs due to technological advantages such as possibilities to adjust contrast, better image quality and transfer capabilities. This study describes the performance indicators during the transition from SFM to FFDM and the characteristics of screen-detected and interval cancers. Methods: Data of the Dutch breast cancer screening program, region North from 2004 to 2010 were linked to The Netherlands Cancer Registry (N = 902 868). Performance indicators and tumour characteristics of screen-detected and interval cancers were compared between FFDM and SFM. Results: After initial screens, recall rates were 2.1% (SFM) and 3.0% (FFDM; P <0.001). The positive predictive values (PPV) were 25.6% (SFM) and 19.9% (FFDM; P = 0.002). Detection rates were similar, as were all performance indicators after subsequent screens. Similar percentages of low-grade ductal carcinoma in situ (DCIS) were found for SFM and FFDM. Invasive cancers diagnosed after subsequent screens with FFDM were more often of high-grade (P = 0.024) and ductal type (P = 0.030). The incidence rates of interval cancers were similar for SFM and FFDM after initial (2.69/1000 vs 2.51/1000; P = 0.787) and subsequent screens (2.30 vs 2.41; P = 0.652), with similar tumour characteristics. Conclusions: FFDM resulted in similar rates of screen-detected and interval cancers, indicating that FFDM performs as well as SFM in a breast cancer screening program. No signs of an increase in low-grade DCIS (which might connote possible overdiagnosis) were seen. Nonetheless, after initial screening, which accounts for 12% of all screens, FFDM resulted in higher recall rate and lower PPV that requires attention

Difficult decisions in the cost-effectiveness analysis of new cancer treatments

The value of cancer treatment varies. In The Netherlands ENDO was formed to reach consensus on the value of treatment with a newly developed tool. Professors Willemse and Tjan-Heijnen, former chairs of this committee, together look at the intrinsic difficulties of valuing new cancer treatments

The influence of endocrine treatments for breast cancer on health-related quality of life

Many hormonal modalities are available for breast cancer treatment, such as selective oestrogen receptor modulators (SERMs), aromatase inhibitors, progestins and luteinising hormone-releasing hormone (LHRH) agonists. The Long-term impact of these endocrine manipulations is an issue, because the duration of adjuvant treatment is still increasing, as is the number of breast cancer survivors. Premature menopause is induced at a young age, and may often be permanent after chemotherapy. The purpose of this review is to provide a literature-based overview of the side effects of endocrine treatment in pre- and postmenopausal breast cancer patients and the influence on HRQoL, especially on sexual functioning. The collection of health-related quality of life (HRQoL) data can result in better treatment recommendations during endocrine therapy. Methods: This review was Limited to prospective randomised studies in English Literature from between 1977 and 2007 and provides an overview of the effects on HRQoL and sexuality of various hormonal treatment in pre- and postmenopausal breast cancer patients, both in the adjuvant and palliative setting. Relevant clinical studies were identified by using the Medline database. Results: HRQoL mostly is severely influenced by chemotherapy and part of these symptoms may be tasting, especially when associated with the induction of premature menopause. Similar symptoms may be encountered during ovarian suppression therapy by LHRH analogs, but they will. usually prove to be reversible. The varying side effect profiles of tamoxifen and aromatase inhibitors did not lead to significant difference in overall HRQoL. HRQoL during progestins and the SERM fulvestrant has been compared to this during aromatase inhibitors, and a large number of studies on HRQoL during endocrine therapy wilt be discussed. (C) 2008 Elsevier Ltd. All rights reserved

Attending the breast screening programme after breast cancer treatment:A population-based study

<p>Introduction: In the Netherlands, breast cancer patients are treated and followed at least 5 years after diagnosis. Furthermore, all women aged 50-74 are invited biennially for mammography by the nationwide screening programme. The relation between the outpatient follow-up (follow-up visits in the outpatient clinic for 5 years after treatment) and the screening programme is not well established and attending the screening programme as well as outpatient follow-up is considered undesirable. This study evaluates potential factors influencing women to attend the screening programme during their outpatient follow-up (overlap) and the (re-)attendance to the screening programme after 5 years of outpatient follow-up.</p><p>Methods: Data of breast cancer patients aged 50-74 years, treated for primary breast cancer between 1996 and 2007 were selected from the Netherlands Cancer Registry and linked to the National Breast Cancer Screening Programme in the Northern region. Cox regression analyses were used to study women (re-) attending the screening programme over time, possible overlap with the outpatient follow-up and factors influencing this.</p><p>Results: In total 11 227 breast cancer patients were included, of whom 19% attended the screening programme after breast cancer treatment, 4.4% within 5 years and 15.4% after more than 5 years. Factors that independently influenced attendance within 5 years as well as more than 5 years after treatment were: interval tumours (HR 0.77; 95% CI 0.61-0.97 and HR 0.69; 95% CI 0.53-0.88, ref: screen-detected tumours), receiving adjuvant radiotherapy (HR 0.65; 95% CI 0.47-0.90 and HR 0.66; 95% CI 0.47-0.93; ref: none) and diagnosis of in situ tumours (HR 1.67; 95% CI 1.25-2.23 and HR 1.39; 95% CI 1.05-1.85; ref: stage I tumours). Non-screen related tumours (HR 0.41; 95% CI 0.29-0.58) and recent diagnosis (HR 0.89 per year; 95% CI 0.86-0.92) were only associated with attendance within 5 years after treatment.</p><p>Conclusion: The interrelation between outpatient follow-up and screening should be improved to avoid overlap and low attendance to the screening programme after outpatient follow-up. Breast cancer patients should be informed that attending the screening programme during the outpatient follow-up is not necessary. (C) 2013 Elsevier Ltd. All rights reserved.</p>

Do screen-detected breast cancers have positive margins less often than clinically detected breast cancers?

<p>Positive tumour margins after breast-conserving surgery (BCS) have been selected as one of the major quality criteria for the surgical treatment of localized primary breast cancer. The national guideline states that the rate of positive margins should not exceed 30% in ductal carcinoma in situ and 20% in invasive cancers. We aimed to determine whether BCS in women with screen-detected breast cancer (SDBC) will have positive margins less often compared with women with clinically detected breast cancer (CDBC). Furthermore, the choice of subsequent therapy is studied when margins were positive after initial BCS. Women 50-75 years of age who underwent BCS for invasive breast cancer between July 2008 and December 2009 were selected from the Netherlands Cancer Registry. Data were merged with the National Cancer Screening Program, regions North and East, to identify women with SDBC. The relation to screening history, clinical and pathological factors was evaluated for correlation with margin status using multilevel analysis. Of 1537 women with an invasive breast cancer, 873 (57%) were diagnosed through the screening programme. SDBCs were significantly smaller (87 vs. 69% T1 tumours, i.e. 2 cm), more often well differentiated (33 vs. 26%), preoperatively confirmed (98 vs. 96%), diagnosed in a nonteaching hospital (60 vs. 66%) and more often had negative lymph nodes (LNs) (80 vs. 68%). In 170 out of 1537 women, the resection margins were positive. Multivariable analysis showed that hospital, tumour size, multifocality, positive LNs and absent preoperative confirmation were predictors of positive margins. No difference was found between women with SDBC and CDBC. Of women with positive margins, 90% underwent additional surgery. Women diagnosed with SDBC do not have a lower risk of having positive margins after BCS than women with CDBC. Although positive margins may occur in 11% of women with invasive tumours, well below the percentage recommended by the national guideline, the presence of encouraging factors by SDBC such as a smaller tumour size, unifocality, negative LNs and the presence of preoperative confirmation should not lead to performing a more sparing excision than is considered usual for comparable CDBC. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.</p>

EARLY-STAGE YOUNG BREAST CANCER PATIENTS:IMPACT OF LOCAL TREATMENT ON SURVIVAL

PurposeIn young women, breast-conserving therapy (BCT), i.e., lumpectomy followed by radiotherapy, has been associated with an increased risk of local recurrence. Still, there is insufficient evidence that BCT impairs survival. The aim of our study was to compare the effect of BCT with mastectomy on overall survival (OS) in young women with early-stage breast cancer.Methods and MaterialsFrom two Dutch regional population-based cancer registries (covering 6.2 million inhabitants) 1,453 women <40 years with pathologically T1N0–1M0 breast cancer were selected. Cox regression survival analysis was used to study the effect of local treatment (BCT vs. mastectomy) stratified for nodal stage on survival and corrected for tumor size, age, period of diagnosis, and use of adjuvant systemic therapy.ResultsWith a median follow-up of 9.6 years, 10-year OS was 83% after BCT and 78% after mastectomy, respectively (unadjusted hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.09–1.72). In N0-patients, 10-year OS was 84% after BCT and 81% after mastectomy and local treatment was not associated with differences in OS (HR 1.19; 95% CI, 0.89–1.58; p = 0.25). Within the N1-patient group, OS was better after BCT compared with mastectomy, 79% vs. 71% at 10 years (HR 1.91; 95% CI, 1.28–2.84; p = 0.001) and in patients treated with adjuvant hormonal therapy (HR 0.34; 95% CI, 0.18–0.66; p = 0.001).ConclusionsIn this large population-based cohort of early-stage young breast cancer patients, 10-year OS was not impaired after BCT compared with mastectomy. Patients with 1 to 3 positive lymph nodes had better prognosis after BCT than after mastectomy

Effect of tamoxifen on the endometrium and the menstrual cycle of premenopausal breast cancer patients

OBJECTIVE: Tamoxifen, a nonsteroidal antiestrogen, is the agent of choice in the treatment of premenopausal receptor-positive breast cancer. This study aimed to investigate the influence of tamoxifen on the menstrual cycle and serum hormone levels and the subsequent endometrial response in premenopausal breast cancer patients. METHODS: In tamoxifen-using breast cancer patients aged 55 years or younger, the last menstrual period was registered, serum hormone levels measured, and the endometrial response visualized by transvaginal ultrasonography every 6 months. Premenopausal status was defined as serum levels of estradiol (E2) 0.10 nmol/L or more and follicle-stimulating hormone 30 IU/L or less. Premenopausal patients with an endometrial response of greater than 12 mm were offered a hysteroscopy and curettage. RESULTS: In 121 patients, a total of 241 measurements were performed. Amenorrhea predicted menopausal status incorrectly in 85 (35%) of the 241 measurements in 47 patients. In 8 of 47 endocrinologic premenopausal patients, transvaginal ultrasonography showed an endometrial response of greater than 12 mm (range,15-29 mm). Histopathology in women with an endometrial thickness of greater than 12 mm showed no malignancy. No relation between E2 levels and endometrial thickness was found. CONCLUSIONS: Tamoxifen leads to a disconnection between clinical and endocrinologic menopause in breast cancer patients aged 55 years or less. In premenopausal patients, tamoxifen has a predominantly antiestrogenic effect on the endometrium without a correlation between E2 levels and endometrial response