scholarly journals Tamoxifen as the first targeted long-term adjuvant therapy for breast cancer

2014 ◽  
Vol 21 (3) ◽  
pp. R235-R246 ◽  
Author(s):  
V Craig Jordan
Keyword(s):  
Breast Cancer ◽  
Adjuvant Therapy ◽  
Ductal Carcinoma ◽  
Success Story ◽  
The Past ◽  
Overview Analysis ◽  
Treat All ◽  
The Impact

Tamoxifen is an unlikely pioneering medicine in medical oncology. Nevertheless, the medicine has continued to surprise us, perform, and save lives for the past 40 years. Unlike any other medicine in oncology, it is used to treat all stages of breast cancer, ductal carcinomain situ, and male breast cancer and pioneered the use of chemoprevention by reducing the incidence of breast cancer in women at high risk and induces ovulation in subfertile women! The impact of tamoxifen is ubiquitous. However, the power to save lives from this unlikely success story came from the first laboratory studies which defined that ‘longer was going to be better’ when tamoxifen was being considered as an adjuvant therapy. This is that success story, with a focus on the interdependent components of: excellence in drug discovery, investment in self-selecting young investigators, a conversation withNature, a conversation between the laboratory and the clinic, and the creation of the Oxford Overview Analysis. Each of these factors was essential to propel the progress of tamoxifen to evolve as an essential part of the fabric of society.

scholarly journals Invasive breast cancer and breast cancer mortality after ductal carcinoma in situ in women attending for breast screening in England, 1988-2014: population based observational cohort study

BMJ ◽  
2020 ◽  
pp. m1570 ◽  
Author(s):  
Gurdeep S Mannu ◽  
Zhe Wang ◽  
John Broggio ◽  
Jackie Charman ◽  
Shan Cheung ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Breast Screening ◽  
Ductal Carcinoma ◽  
Breast Cancer Mortality ◽  
Population Based ◽  
Breast Screening Programme ◽  
Observational Cohort

AbstractObjectiveTo evaluate the long term risks of invasive breast cancer and death from breast cancer after ductal carcinoma in situ (DCIS) diagnosed through breast screening.DesignPopulation based observational cohort study.SettingData from the NHS Breast Screening Programme and the National Cancer Registration and Analysis Service.ParticipantsAll 35 024 women in England diagnosed as having DCIS by the NHS Breast Screening Programme from its start in 1988 until March 2014.Main outcome measuresIncident invasive breast cancer and death from breast cancer.ResultsBy December 2014, 13 606 women had been followed for up to five years, 10 998 for five to nine years, 6861 for 10-14 years, 2620 for 15-19 years, and 939 for at least 20 years. Among these women, 2076 developed invasive breast cancer, corresponding to an incidence rate of 8.82 (95% confidence interval 8.45 to 9.21) per 1000 women per year and more than double that expected from national cancer incidence rates (ratio of observed rate to expected rate 2.52, 95% confidence interval 2.41 to 2.63). The increase started in the second year after diagnosis of DCIS and continued until the end of follow-up. In the same group of women, 310 died from breast cancer, corresponding to a death rate of 1.26 (1.13 to 1.41) per 1000 women per year and 70% higher than that expected from national breast cancer mortality rates (observed:expected ratio 1.70, 1.52 to 1.90). During the first five years after diagnosis of DCIS, the breast cancer death rate was similar to that expected from national mortality rates (observed:expected ratio 0.87, 0.69 to 1.10), but it then increased, with values of 1.98 (1.65 to 2.37), 2.99 (2.41 to 3.70), and 2.77 (2.01 to 3.80) in years five to nine, 10-14, and 15 or more after DCIS diagnosis. Among 29 044 women with unilateral DCIS undergoing surgery, those who had more intensive treatment (mastectomy, radiotherapy for women who had breast conserving surgery, and endocrine treatment in oestrogen receptor positive disease) and those with larger final surgical margins had lower rates of invasive breast cancer.ConclusionsTo date, women with DCIS detected by screening have, on average, experienced higher long term risks of invasive breast cancer and death from breast cancer than women in the general population during a period of at least two decades after their diagnosis. More intensive treatment and larger final surgical margins were associated with lower risks of invasive breast cancer.

scholarly journals Ductal Carcinoma In Situ of the Breast: Can Biomarkers Improve Current Management?

2014 ◽  
Vol 60 (1) ◽  
pp. 60-67 ◽  
Author(s):  
John Bartlett ◽  
Sharon Nofech-Moses ◽  
Eileen Rakovitch
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma In Situ ◽  
Invasive Breast Cancer ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Low Risk ◽  
Diagnostic Biomarkers ◽  
Repeated Calls ◽  
The Impact

Abstract BACKGROUND Screening for invasive cancer has led to a marked increase in the detection of ductal carcinoma in situ (DCIS). DCIS is, if appropriately managed, a low-risk disease which has a small chance of impacting on patient life expectancy. However, despite significant advances in prognostic marker development in invasive breast cancer, there are no validated diagnostic assays to inform treatment choice for women with DCIS. Therefore we are unable to target effective treatment strategies to women at high risk and avoid over-treatment of women at low risk of progression to invasive breast cancer. Paradoxically, one effect of this uncertainty is undertreatment of some women. CONTENT We review current practice and research in the field to identify key challenges in the management of DCIS. The impact of clinical research, particularly on the over and undertreatment of women with DCIS is assessed. We note slow progress toward development of diagnostic biomarkers and highlight key opportunities to accelerate advances in this area. SUMMARY DCIS is a low-risk disease, its incidence is increasing, and current treatment is effective. However, many women are either over- or undertreated. Despite repeated calls for development of diagnostic biomarkers, progress in this area has been slow, reflecting a relative lack of investment of research effort and funding. Given the low event rate in treated patients and the lateness of recurrences, many previous studies have only limited power to identify independent prognostic and predictive biomarkers. However, the potential for such biomarkers to personalize treatment for DCIS is extremely high.

Long-term risk of second malignancies in women with ductal carcinoma in situ or early-stage invasive breast cancer after breast conservation treatment.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12103-e12103
Author(s):  
Carolyn J. Kushner ◽  
Wei-Ting Hwang ◽  
Lawrence J. Solin ◽  
Neha Vapiwala
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Early Stage ◽  
Breast Conservation ◽  
Conservation Treatment ◽  
Breast Conservation Treatment

e12103 Background: Women with ductal carcinoma in situ (DCIS) or early stage breast cancer have a good prognosis after breast conservation treatment (BCT), and are at risk for second malignant neoplasms (SMNs). The long-term risk of SMNs is not well established and carries important public health implications. Methods: A total of 755 women with DCIS or stage I-II invasive breast cancer underwent breast-conserving surgery followed by definitive breast irradiation between 1995 and 2001. Systemic therapy (chemotherapy and/or hormonal therapy) was given to 73% of the patients. We have previously described patient demographics and 15-year oncologic outcomes in detail (Vapiwala, Cancer, 2017). The patient records were reviewed for development of SMNs. SMNs of any anatomic site (other than contralateral breast cancer and basal/squamous cell carcinoma of the skin) were included for analysis. The Kaplan-Meier method was used to determine the rate of SMNs over time. Median follow-up was 13.8 years. Results: The 5-, 10-, and 15-year rates of developing any SMN were 3.6% (95% CI 2.4-5.3%), 7.8% (95% CI 6.0-10.2%), and 12.7% (95% CI 10.2-15.8%). The most common SMNs were uterine (n=12), leukemia/lymphoma (n=11), melanoma (n=10), ovarian (n=9), and lung (n=7). Conclusions: Development of SMNs is a substantial risk for a protracted period of time following BCT. Clinical patterns of specific SMN histologies, locations and time course of development suggest potential opportunities for screening and treatment to guide patient survivorship clinics and protocols.

scholarly journals Long-Term Outcomes of Sentinel Lymph Node Biopsy for Ductal Carcinoma in Situ

2019 ◽  
Vol 3 (4) ◽  
Author(s):  
Peiyin Hung ◽  
Shi-Yi Wang ◽  
Brigid K Killelea ◽  
Sarah S Mougalian ◽  
Suzanne B Evans ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Breast Cancer Mortality ◽  
Breast Conserving Surgery ◽  
Lymph Node Biopsy ◽  
Long Term Outcomes ◽  
Node Biopsy

Abstract The use of sentinel lymph node biopsy (SLNB) for ductal carcinoma in situ (DCIS) is controversial. Using population-cohort data, we examined whether SLNB improves long-term outcomes among patients with DCIS who underwent breast-conserving surgery. We identified 12 776 women aged 67–94 years diagnosed during 2001–2013 with DCIS who underwent breast-conserving surgery from the US Surveillance, Epidemiology, and End Results-Medicare dataset, 1992 (15.6%) of whom underwent SLNB (median follow-up: 69 months). Tests of statistical significance are two-sided. Patients with and without SLNB did not differ statistically significantly regarding treated recurrence (3.9% vs 3.7%; P = .62), ipsilateral invasive occurrence (1.4% vs 1.7%, P = .33), or breast cancer mortality (1.0% vs 0.9%, P = .86). With Mahalanobis-matching and competing-risks survival analyses, SLNB was not statistically significantly associated with treated recurrence, ipsilateral invasive occurrence, or breast cancer mortality (P ≥ .27). Our findings do not support the routine performance of SLNB for older patients with DCIS amenable to breast conservation.

Impact of Routine Pathology Review on Treatment for Node-Negative Breast Cancer

2012 ◽  
Vol 30 (18) ◽  
pp. 2227-2231 ◽  
Author(s):  
Hagen F. Kennecke ◽  
Caroline H. Speers ◽  
Catherine A. Ennis ◽  
Karen Gelmon ◽  
Ivo A. Olivotto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma ◽  
Tumor Biology ◽  
Node Negative ◽  
Node Negative Breast Cancer ◽  
Secondary Pathology ◽  
Cancer Agency ◽  
The Impact ◽  
Pathology Review

Purpose Routine secondary pathology review influences diagnosis and treatment among patients diagnosed with breast cancer. The impact of review on patients with node-negative breast cancer and the nature of the pathology elements leading to management changes are not well described. Methods Patients with node-negative, invasive, or in situ breast cancer and evaluable nodes referred to the British Columbia Cancer Agency during two time periods between 2004 and 2007 were included. Pathologists with expertise in breast cancer reviewed the original reports and slides. Biomarker testing was not routinely repeated. Medical record review was conducted to determine whether original pathology was changed and whether recommended therapy was affected. Results Among 906 eligible patients, 405 (45%) received a pathology review. Univariate comparisons revealed that reviewed patients were younger (P < .001) and more likely to have close margins (P < .001), whereas other characteristics were similar. A total of 102 pathology changes were documented among 81 patients (20%). The most frequently changed elements were grade (40%) and lymphovascular (26%), nodal (15%), and margin (12%) status. These changes resulted in 27 treatment modifications among 25 patients (6%). Treatment changes were primarily related to nodal and margin status, and only two of 27 were related to measurement of tumor biology in women with estrogen receptor–positive, node-negative breast cancer. Conclusion Reported rates of change are significant and warrant routine secondary pathology review among patients with node-negative breast cancer or ductal carcinoma in situ before final treatment is recommended. Review remains relevant in the era of gene expression signatures to determine margin and nodal status.

Impact of Randomized Clinical Trial Results in the National Comprehensive Cancer Network on the Use of Tamoxifen After Breast Surgery for Ductal Carcinoma in Situ

2007 ◽  
Vol 25 (22) ◽  
pp. 3251-3258 ◽  
Author(s):  
Tina W.F. Yen ◽  
Henry M. Kuerer ◽  
Rebecca A. Ottesen ◽  
Layla Rouse ◽  
Joyce C. Niland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
National Comprehensive Cancer Network ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Breast Conserving Surgery ◽  
Clinical Trial Results ◽  
Cancer Network ◽  
The Impact

Purpose The National Surgical Adjuvant Breast and Bowel Project B-24 trial, published in June 1999, demonstrated that tamoxifen after breast-conserving surgery (BCS) and radiotherapy for ductal carcinoma in situ (DCIS) reduced the absolute occurrence of ipsilateral and contralateral breast cancer. We assessed the impact of B-24 on practice patterns at selected National Comprehensive Cancer Network (NCCN) centers. Patients and Methods Tamoxifen use after surgery was examined among 1,622 patients presenting for treatment of unilateral DCIS between July 1997 and December 2003 at eight NCCN centers. Associations of clinicopathologic and treatment factors with tamoxifen use were assessed in univariate and multivariable logistic regression analyses. Results Overall, 41% of patients (665 of 1,622) received tamoxifen. The proportion increased from 24% before July 1, 1999, to 46% on or after July 1, 1999. Factors significantly associated with receipt of tamoxifen included diagnosis on or after July 1, 1999 (odds ratio [OR], 3.85; P < .0001), BCS in patients younger than 70 years (OR, 3.21; P = .0073), no history of cerebrovascular or peripheral vascular disease (OR, 3.13; P = .0071), receipt of radiotherapy (OR, 1.82; P = .0009), and previous hysterectomy (OR, 1.34; P = .0459). Tamoxifen use varied significantly by center, from 34% to 74% after BCS and 17% to 53% after mastectomy (P < .0001). Conclusion Tamoxifen use after surgery for DCIS at NCCN centers increased after presentation of the B-24 results. Rates varied substantially by institution, suggesting that physicians differ in how they weigh the modest reduction in breast cancer risk with tamoxifen against its potential adverse effects in this population.

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