Long Latency Period/Higher Risk

Cigarette smoking and breast cancer risk: a long latency period?

Terry PD, Miller AB, Rohan TE

Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, 1300 Morris Park Avenue, 1301-A, Bronx, NY 10461, USA. pterry@aecom.yu.edu

The association between cigarette smoking and breast cancer risk remains unclear. Few studies have examined cigarette smoking of very long duration as there may not have been a sufficient number of long-term smokers in studies conducted before the 1980s.

Therefore, we examined the association between smoking and breast cancer risk using data from participants in a randomized controlled trial of screening for breast cancer involving 89,835 women aged 40-59 years at recruitment and with up to 40 years of smoking duration at that time.

Women with breast cancer diagnosed through 31 December 1993 were identified by linkage to the Canadian Cancer Database. Cox proportional hazards models were used to estimate rate ratios (RRs) and 95% confidence intervals (CIs). During an average of 10.6 years of follow-up, we observed 2,552 incident cases of breast cancer.

We found a positive association between cigarette smoking and breast cancer risk, driven mainly by women who had smoked for several decades and who, therefore, had commenced smoking many years earlier. Relative to never-smokers, women who had smoked 40 years or more and 20 cigarettes/day or more were at the highest risk (RR = 1.83, 95% CI 1.29-2.61); for women who had commenced smoking 40 years or more before assessment (a measure of smoking latency rather than duration and intensity), the RR was 1.22 (95% CI 0.99-1.59).

Our findings suggest that smoking of very long duration and high intensity may be associated with increased risk of breast cancer. Copyright 2002 Wiley-Liss, Inc.

Int J Cancer 2002 Aug 20;100(6):723-8

PMID: 12209614, UI: 22198207

Long-term Follow-up Post-mastectomy Breast Pain

Long-term follow-up of breast cancer survivors with post-mastectomy pain syndrome

L Macdonald1, J Bruce2, N W Scott2, W C S Smith2 and W A Chambers1

1Department of Anaesthesia, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB25 2ZN, UK

2Department of Public Health, University of Aberdeen, Polwarth Building, Medical School, Foresterhill, Aberdeen AB25 2ZD, UK

Correspondence to: Dr J Bruce, E-mail: j.bruce@abdn.ac.uk

Post-mastectomy pain syndrome (PMPS) is a recognised complication of breast surgery although little is known about the long-term outcome of this chronic pain condition. In 1996, Smith et al identified a prevalence rate of PMPS of 43% among 408 women in the Grampian Region, Northeast Scotland.

The aim of this study was to assess long-term outcome at 7-12 years postoperatively in this cohort of women, to describe the natural history of PMPS and impact of pain upon quality of life. Chronic pain and quality of life were assessed using the McGill Pain Questionnaire (MPQ) and Short Form-36 (SF-36).

Of 175 women reporting PMPS in 1996, 138 were eligible for questionnaire follow-up in 2002. Mean time since surgery was 9 years (s.d. 1.8 years). A response rate of 82% (113 out of 138) was achieved; 59 out of 113 (52%) women reported continued PMPS and 54 out of 113 (48%) women reported their PMPS had resolved since the previous survey in 1996.

Quality of life scores were significantly lower in women with persistent PMPS compared to those women whose pain had resolved. However, for women with persistent PMPS, SF-36 scores had improved over time. Risk factors for persistent PMPS included younger age and heavier weight.

This study found that, of women reporting PMPS in 1996, half of those surveyed in 2002 continued to experience PMPS at a mean of 9 years after surgery.

British Journal of Cancer (2005) 92, 225-230.
doi:10.1038/sj.bjc.6602304 Published online 11 January 2005

Long-term Cognitive Deficits/Dementia From Cancer

Cancer as a Risk Factor for Long-Term Cognitive Deficits and Dementia

Lara H. Heflin, Beth E. Meyerowitz, Per Hall, Paul Lichtenstein, Boo Johansson, Nancy L. Pedersen, Margaret Gatz

Affiliations of authors: Department of Psychology, University of Southern California, Los Angeles, CA (LHH, BEM, NLP, MG); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (PH, PL, NLP, MG); Department of Psychology, Göteborg University, Göteborg, Sweden (BJ)

Correspondence to: Beth E. Meyerowitz, PhD, Department of Psychology, University of Southern California, Los Angeles, CA 90089–1061 (e-mail: meyerow@usc.edu).

Previous studies have shown that cancer survivors frequently experience short-term cognitive deficits, but it is unknown how long these deficits last or whether they worsen over time.

Using a co-twin control design, the cognitive function of 702 cancer survivors aged 65 years and older was compared with that of their cancer-free twins.

Dementia rates were also compared in 486 of the twin pairs discordant for cancer. Cancer survivors overall, as well as individuals who had survived cancer for 5 or more years before cognitive testing, were more likely than their co-twins to have cognitive dysfunction (odds ratio [OR] = 2.10, 95% confidence interval [CI] = 1.36 to 3.24; P<.001 and="" or="2.71," ci="1.47" to="" p="" respectively="">
Cancer survivors were also twice as likely to be diagnosed with dementia as their co-twins, but this odds ratio did not reach statistical significance (OR = 2.0, 95% CI = 0.86 to 4.67; P = .10).

These results suggest that cancer patients are at increased risk for long-term cognitive dysfunction compared with individuals who have never had cancer, even after controlling for the influence of genetic factors and rearing environment.

Journal of the National Cancer Institute, Vol. 97, No. 11, 854-856, June 1, 2005
DOI: 10.1093/jnci/dji137

Long-Term Cardiac Trouble & Adjvt Chemotherapy

Long-Term Cardiac Sequelae in Operable Breast Cancer Patients Given Adjuvant Chemotherapy With or Without Doxorubicin and Breast Irradiation.

Zambetti M, Moliterni A, Materazzo C, Stefanelli M, Cipriani S, Valagussa P, Bonadonna G, Gianni L.

Istituto Nazionale Tumori, Milan, Italy.

PURPOSE: To investigate long-term cardiac sequelae associated with anthracycline use in adjuvant chemotherapy of patients with early breast cancer.

PATIENTS AND METHODS: All 1,000 patients from three prospective trials of adjuvant chemotherapy containing doxorubicin (n = 637, median total dose of 294 mg/m(2)) or not containing the anthracycline (cyclophosphamide, methotrexate, and fluorouracil [CMF] regimen alone, n = 363) were analyzed for the relative incidence of congestive heart failure (CHF) and myocardial infarction (MI) during 14 years of follow-up.

The 462 women continuously free of disease as of February 1996 were recalled, and 355 consented to undergo evaluation including 12-lead ECG and cardiac ultrasound with determination of left ventricular ejection fraction (LVEF) to assess the relative incidence of abnormalities in long-term survivors.

RESULTS: Among the 1,000 patients, there were six cases of CHF and three cases of MI. Cumulative cardiac mortality accounted for 0.4% (doxorubicin-treated = 0.6%; CMF-treated = 0). Eighteen (5%) of the 355 patients undergoing cardiac evaluation after median 11 years of follow-up presented systolic dysfunction as defined by pathologic (
Systolic dysfunction was higher in doxorubicin-treated (15 of 192; 8%) than in CMF-treated patients (three of 150; 2%). Breast irradiation had a significant impact on the occurrence of early CHF (four of 116; 3%), but not on systolic dysfunctions.

CONCLUSION: At longer than 10 years of follow-up, the use of doxorubicin at a total dose commonly applied in regimens of adjuvant chemotherapy does not lead to cardiac clinical sequelae that counter-balance the benefit of treatment in patients with operable breast cancer who may be cured of their disease.

PMID: 11134193 [PubMed – in process]

J Clin Oncol 2001 Jan 1;19(1):37-43

Long-Term Cancer Risk and DES

Long-term cancer risk in women given diethylstilbestrol (DES) during pregnancy

L. Titus-Ernstoff, E. E. Hatch, R. N. Hoover, J. Palmer, E. R. Greenberg, W. Ricker, R. Kaufman, K. Noller, A. L. Herbst, T. Colton, P. Hartge


From 1940 through the 1960s, diethylstilbestrol (DES), a synthetic oestrogen, was given to pregnant women to prevent pregnancy complications and losses. Subsequent studies showed increased risks of reproductive tract abnormalities, particularly vaginal adenocarcinoma, in exposed daughters. An increased risk of breast cancer in the DES-exposed mothers was also found in some studies.

In this report, we present further follow-up and a combined analysis of two cohorts of women who were exposed to DES during pregnancy. The purpose of our study was to evaluate maternal DES exposure in relation to risk of cancer, particularly tumours with a hormonal aetiology. DES exposure status was determined by a review of medical records of the Mothers Study cohort or clinical trial records of the Dieckmann Study. Poisson regression analyses were used to estimate relative risks (RR) and 95% confidence intervals (CI) for the relationship between DES and cancer occurrence.

The study results demonstrated a modest association between DES exposure and breast cancer risk, RR = 1.27 (95% CI = 1.07-1.52). The increased risk was not exacerbated by a family history of breast cancer, or by use of oral contraceptives or hormone replacement therapy. We found no evidence that DES was associated with risk of ovarian, endometrial or other cancer.

British Medical Journal p 126-133, Volume 84, Number 1, January 2001

Long-term Bladder Function After Treatment

Original Article

Long-term bladder function in patients with locally advanced cervical carcinoma treated with neoadjuvant chemotherapy and type 3-4 radical hysterectomy

Pierluigi Benedetti-Panici, M.D. *, Marzio Angelo Zullo, M.D., Francesco Plotti, M.D., Natalina Manci, M.D., Ludovico Muzii, M.D., Roberto Angioli, M.D.

Department of Obstetrics and Gynecology, Università Campus Bio-Medico di Roma, Rome, Italy

email: Pierluigi Benedetti-Panici (p.panici@unicampus.it)

*Correspondence to Pierluigi Benedetti-Panici, Department of Obstetrics and Gynecology, Università Campus Bio-Medico di Roma, Via Longoni 83, 00155 Rome, Italy

Fax: (011) 39 062252294


The objective of the current study was to evaluate the incidence of long-term bladder dysfunction after type 3-4 radical hysterectomy in patients with locally advanced cervical carcinoma treated with neoadjuvant chemotherapy (NACT).

A case-control study was conducted to evaluate the occurrence of long-term bladder dysfunction in 76 patients with International Federation of Gynecology and Obstetrics Stage IB-IIA (> 4 cm), Stage IIB, and Stage III cervical carcinoma who underwent type 3-4 radical hysterectomy after NACT.

Preoperative assessment included acquisition of a standardized urogynecologic history, evaluation of severity of urinary incontinence symptoms, maintenance of a 3-day voiding diary, pelvic examination, urogynecologic physical examination, urodynamic assessment, and estimation of hydronephrosis.

Follow-up was carried out at least 12 months after surgery.

Urinary symptoms (sensory loss, difficult micturition, severe urinary incontinence) were reported by 20 patients (26%).

Eighteen patients (24%) had a normal urodynamic profile, 16 patients (21%) had detrusor overactivity, 22 patients (29%) had urodynamic stress incontinence, 2 patients (2%) had aconctractile detrusor, and 18 patients (24%) had mixed urinary incontinence.

The length of vagina removed was significantly greater among patients who had detrusor overactivity and mixed urinary incontinence compared with patients who had a normal diagnosis.

The observed rate of bladder dysfunction was higher than the corresponding rate reported in the literature (76%). Three main disturbances were found: detrusor overactivity (21%), mixed urinary incontinence (24%), and de novo stress incontinence (21%). Detrusor overactivity was related to a prevalence of hypertonic bladder.

Among patients who underwent type 4 radical hysterectomy, the extent of caudal resection of rectovaginal ligaments and vaginal tissue was found to be more strongly associated with bladder dysfunction than was the extent of lateral parametrial resection.

Despite the fact that 76% of patients had abnormal urodynamic parameters, most patients were satisfied with their voiding condition.

Cancer 2004.

Volume 100, Issue 10 (15 May 2004)

Long-term Adverse Effects w/Testicular Ca Treatment

Friday, 22 February, 2002

Danger legacy of cancer cures

Powerful cancer drugs can cause long-term side-effects

Testicular cancer treatments are now so successful that patients are in more danger from their long-term side effects than from the cancer returning. The major concern of patients whose cancer is in remission tends to be the re-emergence of their original cancer. However, the radical surgery, and powerful chemotherapy and radiotherapy used to treat them can also have lasting effects – a trade-off readily accepted by many patients faced with life-threatening illness.

In the case of some of the most treatable cancers – such as testicular cancer – there is now evidence that there is more chance of becoming ill because of the treatment than of the original cancer coming back. Testicular cancer has cure rates of over 90% in many cases, and even patients with advanced cancer have a reasonable chance.

However, an editorial in the journal the Annals of Oncology warns that doctors should now be looking to reduce the chances that drugs and treatments could harm health later on. Researchers at the West German Cancer Center at the University of Essen looked at 32 testicular cancer patients aged between 30 and 59 who had all been successfully treated wtih chemotherapy. While none had developed different cancers later on – a known risk of chemotherapy – there were alarming cardiovascular side effects of the overall treatment.

Nearly a third had abnormal functioning in part of their heart, although only one, a smoker, had actually suffered a heart attack. Four out of five had elevated cholesterol levels – 25% had developed high blood pressure after chemotherapy. In addition, nearly a quarter had hearing loss, and over a third had some problems with nerve damage. Other Norwegian research, published in the same journal, suggested that chemotherapy and radiotherapy could be causing subtle long-term kidney damage, not enough to produce symptoms by itself, but enough to weaken the organs and perhaps make them vulnerable later in life.

Heart problems

Dr Dirk Strumberg, who led the German research, said it was likely that hormonal and metabolic changes following the treatment – such as lowered testosterone levels – rendered these patients more vulnerable to heart disease. He said: “Testicular cancer patients should be made aware that they might have a greater risk of developing cardiovascular disease that of suffering a recurrence of their cancer or a second malignancy. “They can then take measures to minimise this risk, such as controlling their weight, regulating their blood pressure and cholesterol levels and not smoking.”

Dr Karim Fizazi, of the Institut Gustave Roussy in France, said that research should now turn to ways of limiting the long-term damage caused by treatment.

He said: “In a way, patients have become the victims of the success of treatment. “Long-term side-effects of treatment need to be considered since patients who reach the stage of complete response are likely to live for decades.”

Was this the BBC?

Lombardy (Italy) Approves MJ-based Medicines

Italian region backs medical marijuana

By Rosella Lorenzi

FLORENCE, Italy (Reuters Health) – The council of Italy’s northern region of Lombardy approved on Tuesday a motion in favour of marijuana-based medicines, asking the Italian government and the parliament “to regulate the medical use of cannabis and its derivatives.”

While Canada, the UK, Spain, Australia, Holland and some US states allow the use of marijuana as a treatment for chronic illnesses, at least in clinical trials, in Italy there is no legal way to obtain it but to ask for a magistrate’s ruling.

After listing several scientific studies showing the efficacy of cannabinoids–the active substances in cannabis–in moderating pain, spasms and nausea, the Lombardy document specifies that “the choice to approve the therapeutic use of cannabis should not be included in the debate on the prohibitionist and anti-prohibitionist approach to drugs.”

“Physicians must be able to prescribe their patients the drugs and the therapy they consider most appropriate. Thousands of patients are waiting for the legislation to regulate the therapeutic use of cannabis,” Yasha Reibman, a doctor and regional councillor of the radical party, which presented the motion, said in an official statement.

The Lombardy document “commits the president of the Regional Council and the president of the Region to communicate its content to the government and the parliament.”

But health minister Girolamo Sirchia remained skeptical. “From what we know, cannabis’ benefits are not particularly significant. Also, they are not exclusive: on the market there are already products with the same indications,” he told the daily Corriere della Sera.

Long Island Breast Cancer organizations

Adelphi Breast Cancer Program

LINK: “Founded in 1980 First program in New York State exclusively addressing the psychosocial issues associated with breast cancer

Only New York Statewide Toll-free Breast Cancer Hotline answering almost 4,000 calls each year & over 350,000 web site visits each year

One-hundred specially trained, professionally supervised volunteers, most of whom are breast cancer survivors

Babylon Breast Cancer Coalition
LINK: “The Babylon Breast Cancer Coalition was founded in 1993 when three friends in Babylon, Suffolk County, New York; two of them diagnosed with breast cancer, found they could no longer ignore the statistics. Determined to fight the disease by raising awareness and educating women about breast cancer, the BBCC, with its staff of dedicated volunteers, undertook the task of completing a demographic survey to ascertain the incidence of breast cancer in Babylon”

Breast Cancer Help Inc.

LINK: “a grassroots resource for information & activism in the fight against breast cancer on Long Island, New York. Years of hard work and ongoing effort by breast cancer survivors, their families, friends, & communities have made a serious and positive impact in our fight against cancer. Learn about what you can do to win the battle for our bodies & our lives. If you have been diagnosed with breast cancer, get the support you need to help you overcome the challenges presented by your disease”

 Brentwood/Bayshore Breast Cancer Coalition

LINK: “The Brentwood / Bay Shore Breast Cancer Coalition was initiated as a PTA Council environmental issue with support from church groups. Although we are not Breast Cancer survivors for the most part, we have been moved by people’s pain, & we all suffer the loss of relatives and friends. Through prevention, we hope to protect children & reduce the progress of breast cancer”

 Great Neck Breast Cancer Coalition

LINK: “Since 1992, the Great Neck Breast Cancer Coalition has been dedicated to the battle against breast cancer through education & advocacy of breast cancer research. To further protect future generations, we also advocate breast cancer prevention research & we educate the public on ways to avoid toxic environmental exposures. Along with the battle against breast cancer through outreach, activism and research, we offer support for women who are newly diagnosed

Huntington Breast Cancer Action Coalition

LINK: “Huntington Breast Cancer Action Coalition (HBCAC) is a not-for-profit grassroots organization dedicated to the ultimate eradication of breast cancer through education & awareness. Our mission is to focus on prevention methods while actively helping those who are faced with a positive diagnosis”

  Islip Breast Cancer Coalition

LINK: “The Islip Breast Cancer Coalition is an organization
of volunteers whose goal it is to serve as
a community resource for Islip Town residents
confronted with breast cancer”

 Long Beach Breast Cancer Coalition

LINK for Long Beach, NY
Mission: “Our mission is to promote awareness through education & community outreach; advocacy to increase funding for research into the causes of breast cancer, & for improved methods of detection & treatment; & assistance in securing access to screening, diagnosis, & treatment”

 Manhasset Women’s Coalition Against Breast Cancer

LINK: “The Manhasset Women’s Coalition Against Breast Cancer (“MWCABC”) is an all-volunteer, non-profit charitable organization founded in 1997 to unite the women of Manhasset, Long Island in the fight against breast cancer. MWCABC’s mission is to fund innovative research, increase awareness through education & provide support services to those with breast cancer & related diseases”

 1 in 9 LI Breast Cancer Coaltion

LINK: “committed to fighting the cancer epidemic through education, outreach, environmental advocacy, spearheading changes to legislation affecting cancer issues, &continuously raising money to support innovative epidemiological cancer research projects at Cold Spring Harbor Laboratory

 West Islip Breast Cancer Coalition

LINK: “THE WEST ISLIP BREAST CANCER COALITION FOR LONG ISLAND, INC. is a non-profit, grassroots organization working to eradicate Breast Cancer on Long Island. The WIBCC is dedicated to advancing Breast Cancer research & technology through increased governmental funding which will identify the causes of Breast Cancer”

Low-level, High-frequency Mechanical Signals Enhance…

Low-level, high-frequency mechanical signals enhance musculoskeletal development of young women with low BMD.

Gilsanz V, Wren TA, Sanchez M, Dorey F, Judex S, Rubin C.
Department of Radiology, Childrens Hospital of Los Angeles, University of Southern California, Keck School of Medicine, Los Angeles, California 90027, USA. vgilsanz@chla.usc.edu

The potential for brief periods of low-magnitude, high-frequency mechanical signals to enhance the musculoskeletal system was evaluated in young women with low BMD.

Twelve months of this noninvasive signal, induced as whole body vibration for at least 2 minutes each day, increased bone and muscle mass in the axial skeleton and lower extremities compared with controls.

INTRODUCTION: The incidence of osteoporosis, a disease that manifests in the elderly, may be reduced by increasing peak bone mass in the young. Preliminary data indicate that extremely low-level mechanical signals are anabolic to bone tissue, and their ability to enhance bone and muscle mass in young women was investigated in this study.

MATERIALS AND METHODS: A 12-month trial was conducted in 48 young women (15-20 years) with low BMD and a history of at least one skeletal fracture. One half of the subjects underwent brief (10 minutes requested), daily, low-level whole body vibration (30 Hz, 0.3g); the remaining women served as controls.

Quantitative CT performed at baseline and at the end of study was used to establish changes in muscle and bone mass in the weight-bearing skeleton. RESULTS: Using an intention-to-treat (ITT) analysis, cancellous bone in the lumbar vertebrae and cortical bone in the femoral midshaft of the experimental group increased by 2.1% (p = 0.025) and 3.4% (p
Increases in cancellous and cortical bone were 2.0% (p = 0.06) and 2.3% (p = 0.04) greater, respectively, in the experimental group compared with controls. Cross-sectional area of paraspinous musculature was 4.9% greater (p = 0.002) in the experimental group versus controls.

When a per protocol analysis was considered, gains in both muscle and bone were strongly correlated to a threshold in compliance, where the benefit of the mechanical intervention compared with controls was realized once subjects used the device for at least 2 minute/day (n = 18), as reflected by a 3.9% increase in cancellous bone of the spine (p = 0.007), 2.9% increase in cortical bone of the femur (p = 0.009), and 7.2% increase in musculature of the spine (p = 0.001) compared with controls and low compliers (n = 30).

CONCLUSIONS: Short bouts of extremely low-level mechanical signals, several orders of magnitude below that associated with vigorous exercise, increased bone and muscle mass in the weight-bearing skeleton of young adult females with low BMD.

Should these musculoskeletal enhancements be preserved through adulthood, this intervention may prove to be a deterrent to osteoporosis in the elderly.

J Bone Miner Res. 2006 Sep;21(9):1464-74.

PMID: 16939405 [PubMed – indexed for MEDLINE]