Volume 158Number 4

radiation, chemotherapy) for various types of gyne­cologic malignancies. If a consistent decrease to normalvalues does not occur or if a decrease to normal levelsis followed by a progressive increase in the titer ofB-protein, on the basis of this study, recurrence withor without distant metatasis should be suspected. Aconcerted effort should then be made to locate andidentify the metastases. Consequently, it is our opinionthat the B-protein assay as a cancer management aidmerits serious consideration for further investigation.

REFERENCES

1. Silverberg E, Lubera J. Cancer statistics. CA 1986;36:9-25.2. Cancer trends, 1947-1971. ResidentStaffPhys 1976;90:52­

62.

Serum assay for detection of recurrentcancer

3. Heinonen PK, Tontti K, Koivula T, et aI. Tumour­associated antigen CA 125 in patients with ovarian cancer.Br J Obstet Gynaecol 1985;92:528-31.

4. Nagell JRV Jr. Tumour markers in ovarian cancer. ClinObstet GynecoI1983;10:197-212.

5. Fletcher RH. Carcinoembryonic antigen. Ann Intern Med1986; 104:66-73.

6. Bucovaz ET, Morrison JC, Morrison WC, Whybrew WD.Protein-protein interaction used as assay for detection ofabnormal serum protein of patients with cancer. In: Nie­burgs HE, ed. Third international symposium on detectionand prevention of cancer. 1978 part 2 vol I: 257-69.

7. Bucovaz ET. An assessment ofserological testing for cancerand the B-protein assay. IRCS Med Sci 1983;1l:1-4.

8. Lynn WR, Macleod RM, Morrison JC, Whybrew WD, Bu­covaz ET. Purification and characterization of B-proteinfrom human serum.J Biochem Biophys Meth 1986;12:57­71.

Does family history of breast cancer improve survival amongpatients with breast cancer?

Avima M. Ruder, PhD, Patricia F. Moodie, MS, Norma A. Nelson, PhD, andNung Won Choi, MD, PhD

Winnipeg, Manitoba, Canada

Overall cancer mortality to December 1985 among 291 patients whose breast cancer was diagnosedbetween 1971 and 1974 and who were interviewed shortlyafter diagnosis was 39.9% (116 deaths). In thisstudy population a positive matemal family history was strongly associated with breast cancer: The oddsratiofor patients versus controlsof havinga motherwith breast cancer was 3.32 (95% confidence limits1.64 and 6.72); the odds ratioof havinga mother, sister, or matemal aunt with breast cancer was 1.92(95% confidence limits 1.27 and 2.91). However, family history was not associated with stage at diagnosis,which is the most important survival factor (53.6%of patients with a family history and 51.7% without wereat a localstage at diagnosis). Survival was better, although not significantly so, among women withmaternal relativeswith breast cancer. The relative riskof dying of cancer, adjusted for confounding factors,was 1.40 for women without versus with a family history; the difference in survival was not statisticallysignificant. (AM J OBSTET GVNECOL 1988;158:963-8.)

Key words: Breast neoplasms, familial and genetic; breast neoplasms; etiology

Better survival in patients with breast cancer whohave a positive family history has been observed in sev­eral studies,'? whereas Anderson and Badzioch" found

From the Department of Epidemiology and Biostatistics, ManitobaCancer Treatment and Research Foundation, and the Departmentof Community Health Services, University of Manitoba.

Supported in part by the National Cancer Institute of Canada andin part under National Health Research and Development ProjectNo. 613-1047-30 of the Department of National Health and Wel­fare of Canada. A. M. R. was supported by a fellowship from theManitoba Cancer Treatment and Research Foundation.

Received for publication August 17, 1987; accepted November 20,1987.

Reprint requests:N. W. Choi, MD, PhD, Professor and Director, De­partment ofEpidemiology and Biostatistics,Manitoba Cancer Foun­dation, 100 Olivia St., Winnipeg, Manitoba, Canada R3E OV9.

no improvement in survival for patients with familyhistory. However, an epidemiologic study incorporat­ing interviews ofpatients both with and without a familyhistory of breast cancer has not been reported in theliterature.

For an analysis of long-term survival after the diag­nosis of breast cancer in women with and without afamily history of breast cancer, we supplemented twocase-control interview studies conducted by membersof this department in 1971-1972 and 1973-1974 withcurrent information on patients with breast cancer ab­stracted from the Manitoba Cancer Registry and fromcase records.

We were interested in the following questions: (1) Do

963

964 Ruder et al,

patients with and without a family history of breastcancer differ in age at diagnosis, stage at diagnosis, orother factors? (2) Controlling for other significant de­terminants of survival, do these two groups of patientsdiffer in survival, recurrence of cancer, or other post­diagnostic measures? (3) Does a family history of can­cers other than breast cancer (obtained for the 1973­1974 cohort) have any effect?

Methods

Case selection1971-1972 Cohort. During 1971-1972, information

was obtained from the Manitoba Cancer Registry onall newly diagnosed (first primary cancer) patients withbreast cancer then aged 25 to 54 years and residing inManitoba. Mail questionnaires were sent to those whosephysicians agreed to let them be contacted. For each ofthe 165 patients who participated, three controlsmatched to patients by age ± 3 years were selected fromparticipants in the Manitoba Cytology Registry.

1973-1974 cohort. A consecutive series of 145 newlydiagnosed patients with breast cancer then aged 21 to60 years who resided in metropolitan Winnipeg andwho were recorded in the Manitoba Cancer Registrywas interviewed between 1973 and 1975. Patients wereinterviewed 3 to 5 months after surgery, where possible,or 1 month or more after other treatment. Controlsmatched by age, marital status, and neighborhood res­idence were interviewed within 2 weeks, if possible, ofthe corresponding patient interview. All respondentsgave oral consent to interview. All interviewers werefemale and were not nurses or dieticians (the interviewincluded an extensive dietary history) and had no pre­vious interviewing experience. They were trained notto mention the specific purpose of the study-no men­tion was made of cancer.

File updating. At the end of 1985 the two data fileswere updated with information abstracted from theManitoba Cancer Registry and from case records. Dataincluded stage at diagnosis, disease laterality, date ofdeath for the deceased or date of last contact .for theliving, and current status (for the living: no evidenceof disease, recurrence, development of another pri­mary cancer; for the dead: whether breast cancer me­tastases, another cancer, another disease, or an accidentwas the cause of death). Records were available for 151of 165 patients in the first cohort and 140 of 145 pa­tients in the 1973-1974 cohort.

Separate analyses were undertaken within each datafile for all interview parameters, to ascertain if any in­terview parameters were predictors of survival. In ad­dition, a combined data file was created to analyze pa­rameters present in both data sets, including age atdiagnosis, ethnic origin, birthplace, weight at diagnosis,height, marital status at diagnosis, occupation at diag­nosis, age at menarche, age at first pregnancy, age at

April 1988Am J Obstet Gynecol

menopause (if postmenopausal), whether breast-fed inown infancy, numbers of pregnancies, numbers of live­born offspring, numbers of offspring breast-fed, num­bers of stillbirths, numbers of miscarriages, whethercontraceptive pills were ever taken, whether a closematernal relative (mother, sister, or maternal aunt) hadbeen diagnosed with breast cancer, stage at diagnosis,disease laterality, current status, and date of death, ifdead. The body mass index (weight in kilograms di­vided by the square of height in meters) was used as ameasure of obesity.

Statistical analysis. Comparative survival was as­sessed for all interview parameters as well as stage atdiagnosis and disease laterality.

Survival analyses were stratified by stage. Testing forsignificant effects of study parameters on survival wasby the Mantel-Cox log rank test. In addition, whenstratification was involved a summary test was carriedout while controlling for the stratification variable(stage).

For each analysis we used two measures of survivaltime for patients not known to have died: knownfollow-up (time from diagnosis to last recorded contact)and projected follow-up (assuming that women not re­ported as having died were still alive at the end of 1985).Because the Manitoba Cancer Registry, by law, must benotified of any cancer death in Manitoba, and becauseprovincial death records from the Manitoba Vital Sta­tistics Department are periodically checked against thecancer registry, every in-province death of a patientwith cancer is recorded. Therefore, projected follow­up is a reasonably accurate estimate of true follow-up,which would otherwise be underestimated for livingformer patients who simply do not return for follow­up visits. All results presented here are from the anal­yses with projected follow-up; results from the analyseswith known follow-up (data not shown) are similar.Deaths from causes other than cancer were treated aswithdrawals in the life table analyses."

In addition to analyzing survival, we assessed qualityof survival by comparing women who had disease-freesurvival with those, living or dead, who had experi­enced recurrence, metastasis, or a second primary can­cer, excluding women who had died of causes otherthan cancer. Because the date of recurrence, if any,does not have to be reported to the cancer registry andtherefore was not known for every woman with re­ported recurrence, time to recurrence was not an­alyzed.

To assess the relative contribution of variables foundto be significant in univariate analyses, multivariate Coxproportional hazards tests were performed with cancermortality as the dependent variable. Parallel analyseswere done with the same variables by the use of logisticregression models.

The survival analysis, nonlinear regression, and pro-

Volume 158Number 4

Table I. Breast cancer study populations

December 1985

Updated ICases cases Mortality

1971-1972 165* 151 (91.5%) 63 (41.4%)1973-1974 145t 140 (96.6%) 53 (37.9%)

Total 310 291 (93.9%) 116 (39.9%)

*Age 25 to 54 years, Manitoba residents who completedmail-backquestionnaires. ,

t Age 21 to 60 years, Winnipeg residents interviewed athome.

portional hazards programs used were developed byus and will be described in detail elsewhere.v"

ResultsFor the 1973-1974 cohort, comparisons ofbreast can­

cer risk factors between patients and controls" 10 andsurvival by diet and weight at diagnosis" have beenreported. Survival analyses for parameters other thanfamily history were done for the entire study popula­tion and for an additional group, a 1975-1977 cohortof patients with breast cancer. These results will bereported elsewhere."

Overall cancer mortality to December 1985 was39.9%, with 116 deaths attributed to cancer (metastasesof the original breast cancer or a second primary can­cer) among 291 patients (Table I). In this study pop­ulation a positive maternal family history was stronglyassociated with breast cancer (Table II): the odds ratiofor patients versus controls of having a mother withbreast cancer was 3.32 (95% confidence limits 1.64 and6.72), and the odds ratio of having a mother, sister, ormaternal aunt with breast cancer was 1.92 (95% con­fidence limits 1.27 and 2.91).

We compared the patients with and without a familyhistory of breast cancer to see if they differed in anyparameters associated with either breast cancer risk orprognosis (Table III). In our study population patientswith a positive family history are significantly older atdiagnosis than women with no family history. Thereare no other significant differences.

Stage is the most significant determinant of survival:88 of 139 patients (63.3%) whose disease had spreadto lymph nodes or beyond at the time of diagnosis diedof cancer, compared with 28 of 152 patients (18.4%)diagnosed at an earlier stage (Table IV). The unad­justed odds ratio ofcancer mortality for regional versuslocal stage at diagnosis is 7.49 (95% confidence limits4.39 and 12.78). Although a positive family history ma­terially increased breast cancer risk, it was not associ­ated with either earlier diagnosis (earlier stage) or re­duced survival. Controlling for stage at diagnosis, nosignificant survival differences exist for women with

Does family history improve breast cancer survival? 965

Table II. Family history of breast cancerstudy population

Odds ratiopatient 1control

andMaternal relatives with confidence

breast cancer Family history limits

MotherPatients 25/307 (8.1%) 3.32Controls 12/462 (2.6%) (1.64-6.72)

Sister(s)Patients 16/307 (5.2%) 1.44Controls 17/462 (3.7%) (0.72-2.89)

Aunus)Patients 28/307 (9.1%) 1.92Controls 23/462 (5.0%) (1.08-3.39)

Any maternal relativePatients 57/307 (18.6%) 1.92Controls 49/462 (10.6%) (1.27-2.91)

Table III. Patients with breast cancer with andwithout family history* of breast cancer

No familyParameter history Family history

Age at diagnosis (yr) 47.15 ± 6.72 49.30 ± 6.63t(n = 235) (n = 56)

Age at menarche (yr) 13.24 ± 1.57 13.14 ± 1.62(n = 233) (n = 56)

Age at first pregnancy 24.37 ± 4.50 24.98 ± 5.55(yr) (n = 205) (n = 50)

Age at menopause (yr) 46.26 ± 4.86 47.82 ± 4.97(n = 110) (n = 28)

No. of pregnancies 3.15 ± 2.42 3.54 ± 2.07(n = 235) (n = 56)

No. of live births 2.95 ± 1.85 3.16 ± 1.54(n = 205) (n = 50)

Percentage of infants 55.41 ± 42.81 65.00 ± 41.53breast-fed (n = 197) (n = 48)

Body mass index at 23.80 ± 4.44 23.84 ± 3.75diagnosis (n = 233) (n = 55)

Bilateral cancer? (at 20/235 9156 (16.1%)diagnosis or later) (9.3%)

Herself breast-fed as 179/235 41156 (73.2%)infant? (76.2%)

Ever used contra- 75/235 21156 (37.5%)ceptive pills? (31.9%)

Second primary 20/235 8156 (14.3%)cancer? (9.3%)

Data are mean ± SD. Differences between means weretested by Student's t test for means; X' tests of independencewere applied to the categorical variables.

*Breast cancer reported in mother, sister,or maternal aunt.tProbability of no difference between groups, p< 0.05.

versus without a maternal relative with breast cancer(Table IV). Among those with cancer at a local stage atdiagnosis, the unadjusted odds ratio ofcancer mortalityfor no family history versus family history is 1.16 (95%confidence limits 0.40 and 3.36; NS). Among those atan advanced stage at diagnosis, the odds ratio of cancermortality for no family history versus family history is1.63 (95% confidence limits 0.69 and 3.86; NS).

966 Ruder et al.

Table IV. Cancer mortality among patients with breast cancer

April 1988Am J Obstet Gynecol

AdjustedFamily Cancer mortality Unadjusted odds ratio porportional

Parameter history (December 1985) and confidence limits hazardi

Stage at diagnosisLocal 19.7% 281152 (18.4%) 7.64 4.99Advancedt 18.7% 88/139 (63.3%) (4.47-13.06) (3.23-7.70)

Ethnic originWestern Europe 21.0% 81/219 (37.0%) 1.61 1.17Other 13.9% 35/72 (48.6%) (0.94-2.76) (0.76-1.78)

Body mass indexs25 19.7% 73/204 (35.8%) 1.75 1.26>25 18.2% 43/87 (49.4%) (1.05-2.92) (0.84-1.91 )

OccupationOther§ 22.8% 621171 (36.3%) 1.44 1.06Blue collar/homemaker 14.2% 541120 (45.0%) (0.89-2.32) (0.73-1.53)

Menstrual status at diagnosisPostmenopausal 21.7% 541138 (39.1%) 1.06 1.26Premenopausal 18.3% 621153 (40.5%) (0.66-1.70) (0.87-1.84)

Menarche agesl2 yr 32.3% 33/93 (35.5%) 1.31 1.32~13 yr or unknown 18.2% 83/198 (41.9%) (0.79-2.19) (0.88-1.98)

Family historyYes 19/56 (33.9%) 1.34 1.40No 96/235 (40.9%) (0.73-2.48) (0.86-2.30)

*Cancer mortality risk factors found in 1971-1977 study, plus family history.t Adjusted for the other factors in this table.tDisease has spread to proximal lymph nodes or beyond.§Includes both white-collar workers and women for whom occupation at diagnosis was not stated.

Table V. Cancer mortality among patients with breast cancer at a local stage at diagnosis

Adjustl!dCancer mortality Unadjusted odds ratio proportional

Parameter (December 1985) and confidence limits haUlrd*

Ethnic originWestern Europe 211122 (17.2%) 1.46 1.48Other 7/30 (23.3%) (0.56-3.85) (0.62-3.57)

Body mass indexs25 19/117 (16.2%) 1.79 1.58>25 9/35 (25.7%) (0.72-4.41) (0.71-3.53)

OccupationOthert 12/91 (13.2%) 2.34 2.15Blue-collar/homemaker 16/61 (26.2%) (1.02-5.39) (0.97-4.74)

Menstrual status at diagnosisPostmenopausal 12/70 (17.1%) 1.17 1.19Premenopausal 16/82 (19.5%) (0.51-2.68) (0.56-2.55)

Menarche age13/50sl2 yr (26.0%) 0.49 0.51

~ 13 yr or unknown 151102 (14.7%) (0.21-1.13) (0.24-1.09)Family history !

Yes 5/30 (16.7%) 1.16 0.92No 231122 (18.9%) (0.40-3.36) (0.33-2.55)

*Adjusted for the other factors in this table.tIncludes both white-collar workers and women for whom occupation at diagnosis was not stated.

In the larger (1971-1977) combined study, amongwomen at a local stage at diagnosis, significantly highercancer mortality was found for those of non-WesternEuropean ethnic origins, with a body mass index >25at diagnosis, or whose occupation at diagnosis was blue­collar worker or homemaker. Among those at an ad-

vanced stage at diagnosis, significant survival advan­tages were found for women who were postmenopausalversus premenopausal at diagnosis and for those withearlier (.,;; 12 years) versus later (13 + years) age at men­arche. Therefore in the present study we looked forpossible associations between family history of breast

Volume 158Number 4

Does family history improve breast cancer survival? 967

Table VI. Cancer mortality among patients with breast cancer at an advanced* stage at diagnosis

AdjustedCancer mortality Unadjusted oddsratio proportional

Parameter (December 1985) and confidence limits hazardt

Ethnic originWestern Europe 60/97 (61.9%) 1.23 l.l2Other 28/42 (66.7%) (0.58-2.64) (0.68-1.83)

Body mass indexs25 54/87 (62.1%) l.l5 1.14>25 34/52 (65.4%) (0.56-2.36) (0.70- 1.84)

OccupationOtherj 50/80 (62.5%) 1.09 0.89Blue collar/homemaker 38/59 (64.4%) (0.54-2.18) (0.58-1.37)

Menstrual status at diagnosisPostmenopausal 42/68 (61.8%) l.l4 1.27Premenopausal 46/71 (64.8%) (0.57-2.27) (0.83-1.95)

Menarche ages12 yr 20/43 (46.5%) 2.79 1.85~13 yr or unknown 68/96 (70.8%) (1.33-5.87) (l.l2-3.05)

Family historyYes 14/26 (53.9%) 1.63 1.46No 74/113 (65.5%) (0.69-3.86) (0.82-2.60)

*Disease has spread to proximal lymph nodes or beyond.t Adjusted for the other factors in this table.Uncludes both white-collar workers and women for whom occupation at diagnosis was not stated.

cancer and these cancer mortality risk factors (TableIV), but there were no significant associations.

A multiple Cox proportional hazards test with lengthof survival as the dependent variable incorporatedfamily history, stage at diagnosis, and the five above­mentioned cancer mortality risk factors (Table IV).Separate analyses were done among those at a localstage at diagnosis (Table V) and those at a more ad­vanced stage at diagnosis (Table VI). The multivariateresults are compatible with both the univariate resultsin this study and with the results of the larger study.Parallel multivariate logistic regression analyses withthe same independent variables and cancer mortalityas the dependent variable gave quite similar relativerisks (results not shown).

In the 1973-1974 study, respondents were asked ifthey had any close relatives with cancer of any kind. Asignificantly greater percentage of patients with one ormore relatives with any cancer were at a local stage atdiagnosis, compared with those not reporting any rel­atives with cancer (Table VI).

CommentTrue breast cancer mortality in the Manitoba pop­

ulation is likely to be higher than the mortality observedin our study because of two factors. The protocols ofboth of our original studies excluded the very youngestand very oldest patients. Furthermore, patients refus­ing interviews because they were very ill (and possiblydying soon after), as well as patients who died beforethey could be asked to participate, were excluded fromthe studies.

Obtaining otherwise unverified family histories froman interview subject can introduce several sources ofbias. The subject may not know of all cases of disease,even among close relatives. A patient with cancer maybe more interested in exploring her family's medicalhistory. No correction was made for adopted subjectsor for those whose relatives may have died young ofother causes. With a common cancer such as breastcancer, the chance of two sporadic occurrences in onefamily is not negligible. It is difficult to confirm thediagnosis of a patient's relative reported to have breastcancer, and almost impossible to determine if relativesreported as not having breast cancer have actually beenso diagnosed. However, epidemiologic studies such asthe present one are valuable in pointing the way tohypotheses to be tested in intensive study of all mem­bers of "cancer-prone" (and "not-cancer-prone") fam­ilies.

Our finding of a significantly older mean age at di­agnosis in patients with a family history of breast canceris at odds with the report by Langlands et al.' thatpatients with a family history were significantly youngerthan those without a family history. However, the pa­tients of Langlands et al. were not interviewed. In thecharts, family history may have been noted preferen­tially for younger-than-average patients, or even exclu­sively, as the family history group in that study includesonly 165 of a series of 2998 patients with breast cancer,or 5.5% of the patients (in our study 19.2% of thepatients reported having at least one close maternalrelative with breast cancer). The improved survival wefound in the family history group does agree with the

968 Ruder et al.

results of Langlands et aI., Lynch et al.," and Albanoet al." In the latter two studies, 5-year survival for theirregistry of patients with a family history was comparedwith survival for patients in a published American Col­lege of Surgeons series reported to have similar distri­butions of stage at diagnosis. The family history statusof the American College of Surgeons patients was notnoted, and the analysis was not controlled for stage atdiagnosis or other factors.

Anderson and Badzioch" asked their series of "fa­milial" patients about relatives with breast cancer, butdid not interview their "general" patients. Also, "gen­eral" patients with a family history of breast cancernoted in their hospital records were not excluded fromthe study. Their survival comparison of "familial" and"general" patients, which demonstrated similar survivalrates in both groups, was not controlled for stage.

Our results demonstrate that stage at diagnosis is themost important factor in breast cancer survival, inagreement with a number of previous studies. Al­though the survival advantage among women with afamily history of breast cancer is not statistically sig­nificant, a tendency toward improved survival is indi­cated, especially among women at a more advancedstage at diagnosis. Future studies such as ours, con­troIIing for other breast cancer mortality risk factors,in a larger patient population are certainly called for.Our finding that patients with one or more relativeswith any cancer tended to present at an earlier stageat diagnosis (Table IV) could be due to a greater aware­ness of cancer signs and symptoms, to a more benign

April 1988Am J Obstet Gynecol

or less rapid course of the disease in patients in familiesthat know cancer, or both.

The project of updating these interview studies withthe current case data could not have been accomplishedwithout the assistance of Marie Regan of our depart­ment, and of the entire Records and Registry depart­ment staff.

REFERENCES

1. Langlands AO, Kerr GR, Bloomer SM. Familial breastcancer. Clin Oncol 1976;2:41-5.

2. Lynch HT, Albano WA, Recabaren JA, et al. Survivalin hereditary breast and colon cancer. JAMA 1981;246:1197.

3. Albano WA, Recabaren JA, Lynch HT, et al. Natural his­tory of hereditary cancer of the breast and colon. Cancer1982;50:360-3.

4. Anderson DE, Badzioch MD. Survival in familial breastcancer patients. Cancer 1986;58:360-5.

5. Cutler SJ, Axtell LM. Adjustment of long-term survivalrates for deaths due to intercurrent disease. J Chronic Dis1968;22:485-91.

6. Nelson NA, Moodie PF. A FORTRAN program for Coxproportional hazards survival analysis (in preparation).

7. Nelson NA, Moodie PF. A FORTRAN program for mul­tivariate non-linear regression with particular applicationsto epidemiologic studies (in preparation).

8. Nelson NA, Moodie PF. A FORTRAN program for strat­ified survival analysis (in preparation).

9. Choi NW, Howe GR, Miller AB, et al. An epidemiologicstudy of breast cancer. Am J Epidemiol 1978; 107:510-21.

10. Miller AB, Kelly A, Choi NW, et al. A study of diet andbreast cancer. Am J Epidemiol 1978; 107:499-509.

11. Newman SC, Miller AB, Howe GF. A study of the effectof weight and dietary fat on breast cancer survival time.AmJ EpidemioI1986;123:767-74.

12. Ruder AM, Nelson NA, Moodie PF, Choi NW. Long-termsurvival among breast cancer patients (in preparation).

Bound volumes available to subscribersBound volumes of the AMERICAN JOURNAL OFOBSTETRICS AND GYNECOLOGY are avail­

able to subscribers (only) for the 1988 issues from the Publisher, at a cost of $54.00 ($77.00international) for Vol. 158 (January-June) and Vol. 159 (July-December). Shipping chargesare included. Each bound volume contains a subject and author index and all advertisingis removed. Copies are shipped within 60 days after publication of the last issue in thevolume. The binding is durable buckram with the JOURNAL name, volume number, andyear stamped in gold on the spine. Payment must accompany all orders. Contact The C. V.Mosby Company, Circulation Department, 11830 Westline Industrial Drive, S1. Louis,Missouri 63146, USA; phone (800) 325-4177, ext. 351.

Subscriptions must be in force to qualify. Bound volumes are not available in placeof a regular JOURNAL subscription.