Geographic variation in breast cancer incidence rates in a cohort of U.S. women

F Laden, D et al.

BACKGROUND: Breast cancer mortality and incidence rates vary by geographic region in the United States. Previous analytic studies have measured mortality, not incidence, and have used regional prevalences to control for geographic variation in risk factors rather than adjusting for risk factors measured at the level of the individual. We prospectively evaluated regional variation in breast cancer incidence rates in the Nurses' Health Study and assessed the influence of breast cancer risk factors measured at the individual level. METHODS: The Nurses' Health Study cohort was established in 1976 when 121700 female nurses aged 30-55 years living in 11 U.S. states were enrolled. These states represent all four regions of the continental United States. We identified 3603 incident cases of invasive breast cancer through 1992 (1794565 person-years of follow-up). We calculated relative risks (RRs) adjusted for age and for age and established risk factors (i.e., multivariate-adjusted analysis), comparing California, the Northeast, and the Midwest with the South. RESULTS: For premenopausal women, there was little evidence of regional variation in breast cancer incidence rates, either in age-adjusted or in multivariate-adjusted analyses. For postmenopausal women in California, age-adjusted risk was modestly elevated (RR = 1.24; 95% confidence interval [CI] = 1.05-1.47); after adjusting for age and for established risk factors, the excess rate in California was attenuated by 25% (RR = 1.18; 95% CI = 1.00-1.40). No excess of breast cancer incidence was observed for postmenopausal women in either the Northeast or the Midwest. CONCLUSIONS: Little regional variation in age-adjusted breast cancer incidence rates was observed, with the exception of a modest excess for postmenopausal women in California. Adjustment for differences in the distribution of established risk factors explained some of the excess risk in California.

Journal Of The National Cancer Institute, Vol 89, 1373-1378, Copyright © 1997 by Oxford University Press
Source: http://jncicancerspectrum.oxfordjournals.org/cgi/content/abstract/jnci%3b89/18/1373




History of Psycho-Oncology: Overcoming Attitudinal and Conceptual Barriers

Jimmie C. Holland, MD


ABSTRACT

The formal beginnings of psycho-oncology date to the mid-1970s, when the stigma making the word "cancer" unspeakable was diminished to the point that the diagnosis could be revealed and the feelings of patients about their illness could be explored for the first time. However, a second stigma has contributed to the late development of interest in the psychological dimensions of cancer: negative attitudes attached to mental illness and psychological problems, even in the context of medical illness. It is important to understand these historical underpinnings because they continue to color contemporary attitudes and beliefs about cancer and its psychiatric comorbidity and psychosocial problems. Over the last quarter of the past century, psycho-oncology became a subspecialty of oncology with its own body of knowledge contributing to cancer care. In the new millennium, a significant base of literature, training programs, and a broad research agenda have evolved with applications at all points on the cancer continuum: behavioral research in changing lifestyle and habits to reduce cancer risk; study of behaviors and attitudes to ensure early detection; study of psychological issues related to genetic risk and testing; symptom control (anxiety, depression, delirium, pain, and fatigue) during active treatment; management of psychological sequelae in cancer survivors; and management of the psychological aspects of palliative and end-of-life care. Links between psychological and physiological domains of relevance to cancer risk and survival are being actively explored through psychoneuroimmunology. Research in these areas will occupy the research agenda for the first quarter of the new century. At the start of the third millennium, psycho-oncology has come of age as one of the youngest subspecialties of oncology, as one of the most clearly defined subspecialties of consultation-liaison psychiatry, and as an example of the value of a broad multidisciplinary application of the behavioral and social sciences.

Key Words: psycho-oncology, • cancer, • multidisciplinary treatment approach, • attitudes.

Abbreviations: DSM-III = Diagnostic and Statistical Manual of Mental Disorders, third edition;; HADS = Hospital Anxiety and Depression Scale;; NCCN = National Comprehensive Cancer Network;; PTSD = posttraumatic stress disorder.

Psychosomatic Medicine 64:206-221 (2002) © 2002 American Psychosomatic Society
Source: http://www.psychosomaticmedicine.org/cgi/content/abstract/64/2/206




Meeting Highlights: International Expert Consensus on the Primary Therapy of Early Breast Cancer 2005

A. Goldhirsch, J. H. et al

The ninth St Gallen (Switzerland) expert consensus meeting in January 2005 made a fundamental change in the algorithm for selection of adjuvant systemic therapy for early breast cancer. Rather than the earlier approach commencing with risk assessment, the Panel affirmed that the first consideration was endocrine responsiveness. Three categories were acknowledged: endocrine responsive, endocrine non-responsive and tumors of uncertain endocrine responsiveness. The three categories were further divided according to menopausal status. Only then did the Panel divide patients into low-, intermediate- and high-risk categories. It agreed that axillary lymph node involvement did not automatically define high risk. Intermediate risk included both node-negative disease (if some features of the primary tumor indicated elevated risk) and patients with one to three involved lymph nodes without additional high-risk features such as HER2/neu gene overexpression. The Panel recommended that patients be offered chemotherapy for endocrine non-responsive disease; endocrine therapy as the primary therapy for endocrine responsive disease, adding chemotherapy for some intermediate- and all high-risk groups in this category; and both chemotherapy and endocrine therapy for all patients in the uncertain endocrine response category except those in the low-risk group.

Annals of Oncology 2005 16(10):1569-1583; doi:10.1093/annonc/mdi326
Source: http://annonc.oxfordjournals.org/cgi/content/abstract/16/10/1569




Identification of CGA as a Novel Estrogen Receptor-responsive Gene in Breast Cancer: An Outstanding Candidate Marker to Predict the Response to Endocrine Therapy

Ivan Bièche et al.

The estrogen receptor (ER) status of breast tumors is used to identify patients who may respond to endocrine agents such as tamoxifen. However, ER status alone is not perfectly predictive, and there is a pressing need for more reliable markers of endocrine responsiveness.

Here, we identified the well-known CGA gene (coding for the subunit of glycoprotein hormones) as a new ER-responsive gene in human breast cancer cells. We used a real-time quantitative reverse transcription-PCR assay to quantify CGA mRNA copy numbers in a large series of breast tumors. CGA overexpression (>10 SD above the mean for normal breast tissues) was observed in 44 of 131 (33.6%) breast tumor RNAs, ranging from 20 to 16,500 times the level in normal breast tissues; the highest levels of CGA gene expression were close to those observed in placenta.

Significant links were observed between CGA gene overexpression and Scarff-Bloom-Richardson histopathological grade I+II (P = 0.015), and progesterone (P = 0.0009) and estrogen (P < 10-7) receptor positivity, which suggested that CGA is a marker of low tumor aggressiveness. We observed CGA mRNA overexpression in 44 of 90 (48.9%) ER-positive tumors and in none of the 41 ER-negative tumors. Immunohistochemical studies demonstrated that human chorionic gonadotropin protein was strictly limited to ER-positive tumor cells. Overexpression of the CGA gene was not accompanied by overexpression of the CGB gene.

Our results also suggest that CGA could be a more reliable marker than PS2 and PR for ER functionality and, thus, for endocrine responsiveness. Moreover, the CGA marker has the added value of dichotomizing ER-positive patients into two subgroups of similar size. Specific antibodies directed to secreted human chorionic gonadotropin protein are commercially available, thus facilitating the future application of this marker to the clinical management of breast cancer.

Cancer Research 61, 1652-1658, February 15, 2001 © 2001 American Association for Cancer Research
Source: http://cancerres.aacrjournals.org/cgi/content/abstract/61/4/1652




Behavior Therapy for Depressed Cancer Patients in Primary Care

Hopko, D. R., et al.

Abstract
Major depression is the most common psychiatric disorder among cancer patients and is associated with significant psychosocial impairment and decreased quality of life. Limited research has explored the utility of psychological interventions with these patients and outcome research investigating the potential benefits of behavior therapy among cancer patients with well-diagnosed depression is non- existent. This study was a preliminary clinical trial (n = 6) to assess the effectiveness of a Brief Behavioral Activation Treatment for Depression among depressed cancer patients in primary care (BATD; Lejuez, Hopko, & Hopko, 2001, 2002). Results revealed strong treatment integrity, good patient compliance, excellent patient satisfaction with the BATD protocol, and significant pre-post treatment gains across a breadth of outcome measures assessing depression, quality of life, and medical outcomes. These gains also were associated with strong effect sizes and were maintained at 3-month follow-up. BATD may represent a practical primary care treatment that may remedy problems associated with more traditional psychosocial interventions. Study limitations and future research directions are discussed.


The University of Tennessee
Source: http://web.utk.edu/~dhopko/BAcancer.pdf




Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion

Lee S. Rosen, M.D. et al

BACKGROUND
Treatment with zoledronic acid (Zol) was compared with a dose of 90 mg of pamidronate (Pam) in breast carcinoma (BC) patients with at least 1 osteolytic lesion based on data from a Phase III, randomized trial.

METHODS
Overall, 1130 patients with breast carcinoma who had all types of bone metastases (osteolytic, mixed, or osteoblastic by radiology) were randomized to receive treatment with either 4 mg of Zol or 8 mg of Zol as a 15-minute infusion or 90 mg of Pam as a 2-hour infusion every 3-4 weeks for 12 months. A skeletal-related event (SRE) was defined as a pathologic fracture, spinal cord compression, radiotherapy, or surgery to bone.

RESULTS
Among all patients with BC, the proportion of those who had an SRE (primary endpoint) was comparable between treatment groups (43% of patients who received 4 mg of Zol vs. 45% of patients who received Pam). Among patients who had breast carcinoma with at least 1 osteolytic lesion (n = 528 patients), the proportion with an SRE was lower in the 4-mg Zol group compared with the Pam group (48% vs. 58%), but this did not reach statistical significance (P = 0.058). The time to first SRE was significantly longer in the 4-mg Zol group compared with the Pam group (median, 310 vs. 174 days; P = 0.013). Moreover, multiple-event analysis demonstrated significant further reductions in the risk of developing SREs over the reduction achieved with Pam (30% in the osteolytic subset [P = 0.010] and 20% for all patients with BC [P = 0.037]).

CONCLUSIONS
The current data indicate that treatment with 4 mg of Zol was more effective than 90 mg of Pam in reducing skeletal complications in a subset of patients with breast carcinoma who had at least 1 osteolytic lesion at study entry. Cancer 2004;100:36-43. © 2003 American Cancer Society.


Cancer. Volume 100, Issue 1 , Pages 36 - 43. Published Online: 6 Nov 2003. Copyright © 2003 American Cancer Society
Source: http://www3.interscience.wiley.com/cgi-bin/abstract/106563672/ABSTRACT





Association of hormone replacement therapy to estrogen and progesterone receptor status in invasive breast carcinoma

Wendy Y. Chen, M.D., et al


Keywords
breast carcinoma • hormone replacement therapy • epidemiology • estrogen receptor • progesterone receptor

BACKGROUND
Observational studies and randomized trials have demonstrated that hormone replacement therapy (HRT) increases the recipient's risk of developing breast carcinoma. Because it is known that some breast malignancies are hormonally responsive and that others are not, it has been hypothesized that HRT may be associated with the development of estrogen receptor (ER)-positive/progesterone receptor (PR)-positive breast carcinoma more so than with the development of ER-negative/PR-negative breast carcinoma.

METHODS
The Nurses' Health Study is a prospective cohort study that enrolled 121,700 female registered nurses ages 30-55 years in 1976. In the current study, the authors analyzed 2548 malignancies that developed among eligible postmenopausal women in that cohort between 1980 and 2000 and for which data on ER and PR status were available.

RESULTS
Compared with women who had never used HRT, current long-term users of HRT were more likely to develop ER-positive/PR-positive breast carcinoma (multivariate risk ratio [RR], 1.80; 95% confidence interval [CI], 1.52-2.12) but were not any more likely to develop ER-negative/PR-negative disease (multivariate RR, 1.00; 95% CI, 0.72-1.39). This effect grew stronger with increasing duration of current HRT use and was also more pronounced among women with body mass index < 25 kg/m2. Furthermore, the association between HRT use and ER-positive/PR-positive disease was stronger among patients receiving combined HRT (CHRT) regimens, which included estrogen and progesterone, than among users of estrogen alone (ERT). In addition, tumors tended to develop more quickly in current users of CHRT than in ERT users.

CONCLUSIONS
The finding that current users of HRT were more likely to develop ER-positive/PR-positive tumors than they were to develop ER-negative/PR-negative ones suggests that both endogenous and exogenous hormonal factors may influence breast tumor characteristics. In analyses of the effects of hormonal factors on breast tumor development, ER-positive/PR-positive tumors and ER-negative/PR-negative tumors should be considered separately from each other Cancer 2004. © 2004 American Cancer Society.


Cancer. Volume 101, Issue 7 , Pages 1490 - 1500. Published Online: 13 Aug 2004
Copyright © 2004 American Cancer Society
Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003.
http://www3.interscience.wiley.com/cgi-bin/abstract/109594245/ABSTRACT