Breast Cancer Watch Digest:
Triple Negative Disease Review
The third issue of our newsletter, Breast Cancer Watch Digest, presents a comprehensive review of the the latest, and emerging, treatments for triple negative breast cancer (ER/PR/HER2 negative), exposing myths about triple negative disease, and reviewing the best-evidenced and most promising therapies, including DNA-damaging agents, PARP inhibitors, and the just approved epothilone agent ixabepilone (Ixempra), along with discussion of major clinical trials.
[Learn more . . . ]

Breast Cancer Watch Digest:
Breast Cancer Brain Metastasis Review of the State of the Art
Our new newsletter, Breast Cancer Watch Digest, presents a comprehensive review of the the latest, and emerging, treatments for brain metastasis from breast cancer, covering whole-brain radiotherapy (WBRT), stereotactic radiosurgery, new effective chemotherapies across the blood-brain barrier, TMZ (temozolomide), radiosensitizers, issues in the HER2 / trastuzumab (Herceptin) setting, and the potential benefit of a natural agent, boswellia.
[Learn more . . . ]

Evidencewatch Alert:
LIFT Tibolone Study Halted:
Increased Risk of Stroke
Evidencewatch reports an early termination of the Organon LIFT study investigating tibolone efficacy on new vertebral fractures in elderly osteoporotic women under DSMB and Steering Committee rules. The interim findings reported an increased incidence of ischemic plus hemorrhagic events (strokes) in tibolone treatment group compared to the control group. But the precise and full clinical implications however are not wholly clear.
[Learn more . . . ]

Menopause
Latest WHI Findings
Latest WHI findings clarify the effects of HRT on heart disease, memory, & breast cancer risk.
[Learn more . . . ]

Tibolone: HRT Alternative
Tibolone, already established for bone loss prevention, is a viable alternative to HRT, shown to be as effective as HRT for relief of hot flashes and vaginal dryness, while improving sexual response, with a favorable safety and side effect profile.
[Learn more . . . ]

Issues with Tibolone
Some studies have raised concern about tibolone's effects on endometrial and breast cell proliferation. Evidencewatch has conducted a systematic review of the literature and finds these concerns unwarranted.
[Learn more . . . ]

Vasomotor Symptom Relief
The North American Menopause Society (NAMS) has published an evidence-based review of the treatment of menopausal vasomotor symptoms, especially hot flashes. Evidencewatch here presents and refines the NAMS findings / recommendations.
[Learn more . . . ]

Vaginal Atrophy / Dryness
Post-menopausal diminished estrogen levels result in numerous physiologic vaginal tissue changes (reduced blood flow and mucosal thickness, increased pH level) manifesting primarily as vaginal dryness. Evidencewatch critically reviews the literature, presenting best practice guidelines for treatment of vaginal atrophy / dryness.
[Learn more . . . ]

No Surrender Forum Debuts
(new) The newly launched website
No Surrender Breast Cancer Support, designed and run by two-time breast cancer survivor and writer Gina, brings a professionally sophisticated and well-organized resource of exceptional value to all women with breast cancer. The main site is supplemented by an outstanding information-rich discussion forum, the
No Surrender Message Board moderated by Gina herself, as well as by an uncommonly inspiring personal
No Nosurrender Blog.
Strongly recommended.
[Visit No Surrender. . . ]

Melatonin & Breast Cancer
(new) New findings show that melatonin (1) is a radioprotector agent, protecting against the organ-injury of radiation and radiotherpy; (2) protects against adriamycin-induced cardiotoxicity as well as enhancing its antitumor activity; (3) shows positive anti-breast cancer activity by decreasing aromatase activity and expression in MCF-7 cells; (4) may reduce cancer-related mortality.
[Learn more . . . ]

OCs & Breast Cancer
(new) Recently there appeared a widely cited study on oral contraceptives (OCs) use and breast cancer risk. The principle author, Chris Kahlenborn, is a former US Congressman and self-acknowledged opponent of all forms of artificial contraception, and is on the advisory board of the anti-choice Christian organization Concerned Women for America which actively lobbies for legislation recognizing the claimed abortion-breast cancer link. However, the study, besides the author's predisposition, suffers from serious methodological flaws, and the charged issue needs to examined in a broader scientific perspective.
[Learn more . . . ]

Melatonin & Breast Cancer
(new) New findings show that melatonin (1) is a radioprotector agent, protecting against the organ-injury of radiation and radiotherpy; (2) protects against adriamycin-induced cardiotoxicity as well as enhancing its antitumor activity; (3) shows positive anti-breast cancer activity by decreasing aromatase activity and expression in MCF-7 cells; (4) may reduce cancer-related mortality.
[Learn more . . . ]

Inflammatory Breast Cancer
IBC Watch
(new) This new site provides an evidence-based research update on inflammatory breast cancer (IBC), focusing on new and emerging treatments.
[Learn more . . . ]

Flaxseed / Lignans
and Breast Cancer
(new) A new study found that dietary flaxseed (daily intake of 25g flaxseed-containing muffin) reduced two tumor biological markers used to measure cancer cell growth, and increased apoptosis, suggesting that dietary flaxseed has the potential to reduce tumor growth in patients with breast cancer.
[Learn more . . . ]

Breast Cancer
Aromatase Inhibitors (AIs)
A promising new breast cancer therapy, the aromatase inhibitors (AIs), exhibits higher efficacy, tolerability and safety than the standard antiestrogen Tamoxifen, with additional potential benefits in breast cancer prevention, lipids and bone metabolism, and without increased risk of endometrial cancer and thromboembolism.
[Learn more . . . ]

Depression
Adult Depression & Self Harm
By now, the association between suicidal ideation and risk of self-harm with SSRI antidepressants in children and adolescents is well known, but some studies have raised similar questions of safety and efficacy in adults.
[Learn more . . . ]

Osteoporosis
Low-Dose Steroids and Bone Health
New findings suggest that even low doses of prednisone (5 mg per day) suppresses several bone formation indices in postmenopausal women and may reduce bone repair / renewal, with potentially adverse effects on bone mass and/or bone strength.
[Learn more . . . ]

Evidencewatch Exclusive:
Gardasil Cervical Vaccine
Unresolved Safety Issues
Evidencewatch has obtained an internal FDA background document that suggests that there are serious and unresolved safety and efficacy concerns, and given this, release to market of Merck's Gardasil HPV vaccine may have been premature.
[Learn more . . . ]

Flawed Study Watch, No. 1 :
PPIs ( Proton pump Inhibitors) Increase Hip Fracture Risk
In a recent case-control study in JAMA¹, University of Pennsylvania researcher Yu-Xiao Yang and colleagues examined the UK-based General Practice Research Database, concluding that long-term PPI therapy was associated with an increased hip fracture risk. But our critical appraisal found some potentially serious methodological compromises in the study and hence it may be insuffcient to support this claim:
(1) The authors failed to control for use of calcium supplements; without calcium supplement use data, there may have been suboptimal, or little or no essential use of calcium supplements.
(2) Hip-fracture cases and controls exhibited potentially confounding between-group differences, with cases more likely to have used psychotropics like anxiolytics, antiepileptics, antidepressants, antipsychotics, and antiparkinsonian agents; yet psychtropics are independently associated with hip fracture risk^2,3.
(3) In addition, corticosteriod use was higher in cases than controls, but there is a well-known increased fracture risk during oral corticosteroid therapy⁴.
(4) There were also additional potentially confounding between-group differences in health, with cases more likely to suffer from dementia, seizure disorders, and impaired mobility among others.

Given the above unresolved issues, further studies are required to be dispositive on the association between PPI use and the risk of osteoporosis and fracture.

1. Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. Apr 4 2007;297(13):1429.
2. Takkouche B, Montes-Martinez A, Gill SS, Etminan M. Psychotropic Medications and the Risk of Fracture: A Meta-Analysis. Drug Saf. 2007 ;30 (2):171-84.
3. Genever RW, Downes TW, Medcalf P. Fracture rates in Parkinson's disease compared with age- and gender-matched controls: a retrospective cohort study. Age Ageing. Jan 2005;34(1):21-4.
4. Van Staa, TP, Leufkens HGM, Abenhaim L, and Cooper C. Use of oral corticosteroids and risk of fracture. J Bone Miner Res. 2000;15:993-1000.

Smoke Watch:
Secondhand Smoke and
Smoking Cessation
The Surgeon General issued (6/27/06) a comprehensive scientific report showing that there is no risk-free level of exposure to secondhand smoke: breathing even small amounts during short periods of exposure is hazardous to the health of nonsmokers: the risk of developing heart disease increases by 25 to 30% and of lung cancer by 20 to 30%. And nearly half of all nonsmoking Americans are still regularly exposed to secondhand smoke.
[Learn more . . . ]

Bisphosphonate Warning
Both Oral and IV Bone Agents
Associated with Jaw Osteonecrosis
There appears to be increased incidence of osteonecrosis of the jaw (ONJ) with prolonged bisphosphonate administration. Although it was thought that the association was restricted to IV-administered agents like zoledronic acid (Zometa) and pamidronate (Aredia), it now appears that oral bisphosphonates such as alendronate (Fosamax) and risedronate (Actonel) exhibit the same adverse potential.
To learn more:
For our technical coverage see Osteoporosis Watch and for implications with respect to breast cancer therapy, see Breast Cancer Watch. There is also consumer-oriented coverage at: Consumer Alert: Osteoporosis Drugs - A Pain in the Jaw?


Cardiovascular Health
Lp(a) and Cardiovascular Risk:
For decades since its discovery, the pathophysiological role of Lp(a) in cardiovascular disease the subject of controversy, especially as to risk, assessment, and intervention.
[Learn more . . . ]

Optimal INR:
Several recent findings have critically clarified the optimal range of anticoagulation required to avoid excess mortality.
[Learn more . . . ]

Hawthorn for (CHF)
Chronic Heart Failure:
Several studies strongly suggest a significant cardioprotective effect of Hawthorn extract.
[Learn more . . . ]

Coenzyme Q10:
Evidencewatch notes that the antioxidant Coenzyme Q10 (CoQ10) has demonstrated efficacy and benefit in cardiovascular disease, especially hypertension, coronary artery disease, hyperlipidemia, and heart failure.
[Learn more . . . ]

Herbal/Warfarin Interaction:
Correcting the Record:
Despite anecdotal claims to the contrary, recent evidence has found that Coenzyme Q10 (CoQ10) and Ginkgo biloba do not influence the clinical effect of warfarin.
[Learn more . . . ]

Strontium Ranelate (PROTELOS):
Strontium ranelate, a unique dual action anti-osteoporotic agent (PROTELOS from Servier Laboratories) received (Sept 21, 2004) marketing authorization across 27 European countries, including the UK. It is now available in the UK for the treatment of postmenopausal osteoporosis to reduce the risk of both vertebral and hip fractures.

Clinical studies demonstrate its efficacy in both increasing bone mineral density and in the reduction of non-vertebral, including hip, as well as vertebral, fractures, with no appreciable adverse effects.
[Learn more . . . ]

Colorectal Cancer (CRC):
Dairy and Calcium
The recent study of Cho et al. (Natl Cancer Inst: Dairy foods, calcium, and colorectal cancer: a pooled analysis of 10 cohort studies) provides new evidence that higher milk and calcium consumption is associated with a lower risk of colorectal cancer.

Colorectal Cancer (CRC)
New Era of Treatment:
At the 94th AACR Meeting a promising new therapy for metastatic CRC based on angiogenesis inhibition was presented (The Avastin Trial) using the bevacizumab agent.
(See also our Primer on Angiogenesis).   
[Learn more . . . ]