2
1004 LETTERS TO THE EDITOR JULY 2001–VOL. 49, NO. 7 JAGS hypercholesterolemia, and healthy siblings of patients with premature cardiovascular disease. 3–5 Our data show that F is safe and effective in a group representative of a larger population, namely high-risk subjects with a history of cardiovascular disease, thus broadening the spectrum of its potential applications. Interestingly, five patients had mild hyperhomocysteinemia, whereas the remaining five had values in the upper normal range. Although the defini- tion and classification of hyperhomocysteinemia is still controversial, F supplementation appears to be beneficial not only in patients with severe hyperhomocysteinemia, but also in those with mild hyperhomocysteinemia or even in those with normal Hcy. This is confirmed by the obser- vation that relatively low baseline Hcy:creatinine ratios still account for a significant proportion of the changes in Hcy, SBP, and PP. Interestingly, the effects of F on PWV and blood pressure are additive to those already achieved by con- ventional pharmacological treatment with cardioactive drugs. Second, PWV is a marker of cardiovascular risk as it relates to the presence and severity of atherosclerosis. 6 Therefore, its reduction following F supplementation indi- cates not only a modification of arterial function, but also probable cardiovascular disease risk reduction. Third, the Hcy lowering is associated with a parallel re- duction of both SBP and PP, two established cardiovascular risk factors, thus providing substantial cardioprotection by reducing both arterial impedance and cardiac afterload. Moreover, the Hcy:creatinine ratio is a predictor of the BP changes, thus potentially allowing the identification of the “responders” versus “nonresponders” to F supplementation. The limitations of our study are related to its open de- sign and the limited number of subjects. Therefore, large- based randomized controlled trials are needed to confirm that our findings would result in a reduction of cardiovas- cular endpoints. ACKNOWLEDGMENTS We thank Ms. Tracy Dew for her technical support. Arduino A. Mangoni, MD Emma Ouldred, RGN, BSc Cameron G. Swif, PhD, FRCP Stephen H.D. Jackson, MD, FRCP Department of Health Care of the Elderly Guy’s, King’s, and St Thomas’ School of Medicine King’s College London, United Kingdom Ruth P. Draper, PhD Roy A. Sherwood, DPhil Department of Clinical Biochemistry King’s College Hospital London, United Kingdom Michelle Lambert-Hammill, MSc Anthony S. Wierzbicki, MD, DPhil Department of Chemical Pathology St Thomas’ Hospital London, United Kingdom REFERENCES 1. Hankey GJ, Eikelboom JW. Homocysteine and vascular disease. Lancet 1999; 354:407–413. 2. Upchurch GR, Welch GN Jr, Fabian AJ et al. Homocyst(e)ine decreases bio- available nitric oxide by a mechanism involving glutathione peroxidase. J Biol Chem 1997;272:17012–17017. 3. Bellamy MF, McDowell IF, Ramsey MW et al. Oral folate enhances endothelial function in hyperhomocysteinaemic subjects. Eur J Clin Invest 1999;29:659–662. 4. Verhaar MC, Wever RM, Kastelein JJ et al. Effects of oral folic acid supple- mentation on endothelial function in familial hypercholesterolemia. Circula- tion 1999;100:335–338. 5. Vermeulen EGJ, Stehouwer CDA, Twisk JWR et al. Effect of homocysteine- lowering treatment with folic acid plus vitamin B 6 on progression of subclini- cal atherosclerosis: A randomised, placebo-controlled trial. Lancet 2000;355: 517–522. 6. Lehmann ED. Clinical value of aortic pulse-wave velocity measurement. Lancet 1999;354:528–529. BREAST CANCER IN OLDER WOMEN To the Editor: Breast cancer is the commonest type of can- cer in women, the first cause of death in women age 65 to 79 and the second in women age 80 and older. 1 Its inci- dence increases with advancing years. At the same time, the proportion of older people in the general population is increasing and the reported age-adjusted incidence of breast malignancy is increasing correspondingly. It is im- portant to notice that women age 70 will live, on average, for an additional 14 years and those age 80 have 8 more years of life. 2 However, there are still not enough data on older women with breast cancer because patients over the age of 70 have usually been excluded from randomized clinical trials because of their age. During a 10-year period (1988–1998), 3,841 patients were examined for breast disease in our Breast Unit. Women age 70 and older represented less than 5% of the total num- ber of women examined (Figure 1). Primary breast cancer was found in 683 (17.8%) patients. The number of patients with breast cancer who were age 70 and older was 137, or 20.1% of the total number of breast cancers found. Consid- ering the percentage of breast cancers found among each age group examined, almost 8 out of 10 women age 70 and older that were examined were found to have breast cancer (Figure 1). The latest shows clearly that older women usually seek medical help only when they have an obvious carci- noma or the disease is already locally advanced. Of those 137 patients, 78 women between age 70 and 93 had surgical treatment in our Breast Unit and complete data were available for analysis. Only a few of our patients (5%) appeared with a nonpalpable, mammographically detected breast cancer Figure 1. Percentage of breast cancer patients in each age group of women examined.

Breast Cancer in Older Women

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1004

LETTERS TO THE EDITOR

JULY 2001–VOL. 49, NO. 7 JAGS

hypercholesterolemia, and healthy siblings of patients withpremature cardiovascular disease.

3–5

Our data show that Fis safe and effective in a group representative of a largerpopulation, namely high-risk subjects with a history ofcardiovascular disease, thus broadening the spectrum ofits potential applications. Interestingly, five patients hadmild hyperhomocysteinemia, whereas the remaining fivehad values in the upper normal range. Although the defini-tion and classification of hyperhomocysteinemia is stillcontroversial, F supplementation appears to be beneficialnot only in patients with severe hyperhomocysteinemia,but also in those with mild hyperhomocysteinemia or evenin those with normal Hcy. This is confirmed by the obser-vation that relatively low baseline Hcy:creatinine ratiosstill account for a significant proportion of the changes inHcy, SBP, and PP. Interestingly, the effects of F on PWV andblood pressure are additive to those already achieved by con-ventional pharmacological treatment with cardioactive drugs.

Second, PWV is a marker of cardiovascular risk as itrelates to the presence and severity of atherosclerosis.

6

Therefore, its reduction following F supplementation indi-cates not only a modification of arterial function, but alsoprobable cardiovascular disease risk reduction.

Third, the Hcy lowering is associated with a parallel re-duction of both SBP and PP, two established cardiovascularrisk factors, thus providing substantial cardioprotection byreducing both arterial impedance and cardiac afterload.Moreover, the Hcy:creatinine ratio is a predictor of the BPchanges, thus potentially allowing the identification of the“responders” versus “nonresponders” to F supplementation.

The limitations of our study are related to its open de-sign and the limited number of subjects. Therefore, large-based randomized controlled trials are needed to confirmthat our findings would result in a reduction of cardiovas-cular endpoints.

ACKNOWLEDGMENTS

We thank Ms. Tracy Dew for her technical support.

Arduino A. Mangoni, MDEmma Ouldred, RGN, BSc

Cameron G. Swif, PhD, FRCPStephen H.D. Jackson, MD, FRCP

Department of Health Care of the ElderlyGuy’s, King’s, and St Thomas’ School of Medicine

King’s CollegeLondon, United Kingdom

Ruth P. Draper, PhDRoy A. Sherwood, DPhil

Department of Clinical BiochemistryKing’s College Hospital

London, United Kingdom

Michelle Lambert-Hammill, MScAnthony S. Wierzbicki, MD, DPhilDepartment of Chemical Pathology

St Thomas’ HospitalLondon, United Kingdom

REFERENCES

1. Hankey GJ, Eikelboom JW. Homocysteine and vascular disease. Lancet 1999;354:407–413.

2. Upchurch GR, Welch GN Jr, Fabian AJ et al. Homocyst(e)ine decreases bio-available nitric oxide by a mechanism involving glutathione peroxidase. J BiolChem 1997;272:17012–17017.

3. Bellamy MF, McDowell IF, Ramsey MW et al. Oral folate enhances endothelialfunction in hyperhomocysteinaemic subjects. Eur J Clin Invest 1999;29:659–662.

4. Verhaar MC, Wever RM, Kastelein JJ et al. Effects of oral folic acid supple-mentation on endothelial function in familial hypercholesterolemia. Circula-tion 1999;100:335–338.

5. Vermeulen EGJ, Stehouwer CDA, Twisk JWR et al. Effect of homocysteine-lowering treatment with folic acid plus vitamin B

6

on progression of subclini-cal atherosclerosis: A randomised, placebo-controlled trial. Lancet 2000;355:517–522.

6. Lehmann ED. Clinical value of aortic pulse-wave velocity measurement. Lancet1999;354:528–529.

BREAST CANCER IN OLDER WOMEN

To the Editor:

Breast cancer is the commonest type of can-cer in women, the first cause of death in women age 65 to79 and the second in women age 80 and older.

1

Its inci-dence increases with advancing years. At the same time,the proportion of older people in the general population isincreasing and the reported age-adjusted incidence ofbreast malignancy is increasing correspondingly. It is im-portant to notice that women age 70 will live, on average,for an additional 14 years and those age 80 have 8 moreyears of life.

2

However, there are still not enough data onolder women with breast cancer because patients over theage of 70 have usually been excluded from randomizedclinical trials because of their age.

During a 10-year period (1988–1998), 3,841 patientswere examined for breast disease in our Breast Unit. Womenage 70 and older represented less than 5% of the total num-ber of women examined (Figure 1). Primary breast cancerwas found in 683 (17.8%) patients. The number of patientswith breast cancer who were age 70 and older was 137, or20.1% of the total number of breast cancers found. Consid-ering the percentage of breast cancers found among each agegroup examined, almost 8 out of 10 women age 70 andolder that were examined were found to have breast cancer(Figure 1). The latest shows clearly that older women usuallyseek medical help only when they have an obvious carci-noma or the disease is already locally advanced.

Of those 137 patients, 78 women between age 70 and93 had surgical treatment in our Breast Unit and completedata were available for analysis.

Only a few of our patients (

5%) appeared with anonpalpable, mammographically detected breast cancer

Figure 1. Percentage of breast cancer patients in each age groupof women examined.

JAGS JULY 2001–VOL. 49, NO. 7

LETTERS TO THE EDITOR

1005

because women of this age very rarely have screeningmammography. However, the usefulness of mammogramsin primary detection of breast cancer in older women hasbeen proved by epidemiological studies.

3

Most of our patients underwent a modified radicalmastectomy (75.6%), with the rest of them treated withconservative surgery. Tumor size ranged from 0.6 cm to15 cm (median 3.7 cm). The commonest histological typewas ductal carcinoma (83.3%). Positive axillary lymphnode status was found in 25% of our patients. Estrogen-receptor-positive tumors were found in 55 cases (70.5%)and positive progesterone receptor status was found in 44cases (56.4%).

The majority of patients (91%) received adjuvantTamoxifen and 11.5% also had radiotherapy. The totalsurvival for all our patients estimated by Kaplan-Meier’smethod and Log-rank test was, on average, 73 months.The survival of women with and without invaded axillarylymph nodes was 68 and 98 months respectively, showinga statistically significant difference between those twogroups (

P

.0094) in favor of patients without axillarynode involvement.

Even though there is a general opinion that olderwomen seem to have a good prognosis with breast cancer,many studies have shown opposite findings, explained bya possible age-related immunodeficiency.

4

Therefore, treat-ment decisions should not differ from those of youngerwomen and surgical treatment—mastectomy or breast con-servation with appropriate axillary surgery—should not beavoided if it is recommended. This surgical management en-sures optimal locoregional disease control and survival.

5

Most older women’s breast cancers are positive forhormone receptors. This is very important because adju-vant hormonal therapy (tamoxifen or aromatase inhibi-tors) is a valuable treatment for older patients, withoutmajor side effects. During the last decade, many authorshave also studied the efficacy of breast cancer treatment withtamoxifen only, but even though primary endocrine therapycan achieve a tumor response in up to 65% of patients, thereis a significantly higher local disease relapse (up to 40%)with tamoxifen monotherapy compared with surgery.

6

As for other adjuvant treatment modalities, it hasbeen shown that older women tolerate radiotherapy aswell as younger patients do;

7

chemotherapy should also beconsidered in older patients who are in good health and athigh risk for cancer recurrence.

8

In conclusion, older women should have regular breastexamination and mammography because of the high inci-dence of breast cancer in this age group. Treatment shouldbe as effective as that of younger patients. The surgical pro-cedure of choice (conservative surgery or mastectomy) fol-lowed by hormonal therapy and possibly radiotherapyshould be used in all ages. When surgery is contraindicateddue to serious concomitant health disorders, hormonaltherapy with close follow-up is a valuable option.

Christos Markopoulos, MD, MPhilEfstratios Kouskos, MDMandas Dimitrios, MD

Konstantinos Kontzoglou, MDHarilaos Pappis, MD

Antonios Galanos, MScHelen Gogas, MD

Breast Unit–Second Department of Propedeutic SurgeryAthens University Medical School

Laiko General HospitalAthens, Greece

REFERENCES

1. Muir C, Waterhouse J, Mack T. Cancer Incidence in Five Continents. IARCScientific Publication, Vol. 5. Lyon: IARC, 1987, pp 574–580.

2. McKenna RJ. Clinical aspects of cancer in the elderly. Cancer 1994;74:2107–2117.3. Baker LH. Breast cancer detection demonstration project: Five year summary

report. Can J Clin Invest 1982;32:194.4. McCarty KS, Siwa JS, Cox EB et al. Relationship of age and menopausal status

to estrogen receptor content in primary carcinoma of the breast. Ann Surg1983;197:123–127.

5. Black MM, Barclay TH, Hankey BF. Prognosis of breast cancer utilizing histo-logic characteristics of the primary tumor. Cancer 1975;36:2048–2055.

6. Robertson JFR, Ellis IO, Elston CW et al. Mastectomy or tamoxifen as initialtherapy for operable breast cancer in elderly patients: 5-year follow up. Eur JCancer 1991;28A:908–910.

7. Swanson R, Sawicka J, Woods W. Treatment of carcinoma of the breast in theolder geriatric patient. Surg Gynecol Obstet 1991;173:465–469.

8. VanDalsen AD, DeVries JE. Treatment of breast cancer in elderly patients.J Surg Oncol 1995;60:80–82.

THE CUMULATIVE EFFECTS OF SOCIAL CLASS ON MENTAL STATUS DECLINE

To the Editor:

Studies have shown that lower educationalachievement is associated with greater decline in Mini-Mental State Examination (MMSE) scores.

1,2

Theories toexplain this phenomenon include biological, confounding,and detection bias.

3–6

Education, however, is a marker ofsocial class. It is conceivable that the greater decline inmental status associated with less education may in part bedue to the greater social adversities and stress faced by in-dividuals of lower social class.

7,8

If this alternative expla-nation is true, one would expect other social class markersto be associated with mental status decline and for there tobe a cumulative effect of adversity. To investigate this pos-sibility we determined whether income and work historyalso predict decline in MMSE scores and to what extentthe effects of low education, low income, and having neverhad skilled work are cumulative.

The potential participants were the 1,103 persons en-rolled in Project Safety, a previously described probabilitysample of older Connecticut residents.

9

Our study includesthe 785 participants who completed a baseline, face-to-face, 3-year telephone version of the MMSE.10 The primaryoutcome was a decline of three or more points. Participantswho required a proxy to complete the 3-year interviewwere considered to have MMSE decline. Cutoff points forall three markers of social class (education, annual income,and work history) were chosen to compare the most disad-vantaged third with the rest of the participants. For in-come, we imputed values for 12% of the participants whohad missing data. To determine the cumulative effects ofsocial class adversity, we created a composite score. Onepoint each was assigned for having an eighth grade or lesseducation, having an annual income of $7,000 or less, andhaving never worked or having had work that requiredonly minimal skills. Scores ranged from 0 to 3. Logistic re-gression was performed with education, annual income,and work history in one model and the adversity score in