CEBP Translational Cancer Medicine 2008: Cancer Clinical Trials and Personalized Medicine
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Cell Growth & Differentiation
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chen, Y.
Right arrow Articles by Mao, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, Y.
Right arrow Articles by Mao, Y.
Cancer Epidemiology Biomarkers & Prevention Vol. 8, 855-861, October 1999
© 1999 American Association for Cancer Research

Review

Epidemiology of Contralateral Breast Cancer1

Yue Chen2, Wendy Thompson, Robert Semenciw and Yang Mao

Department of Epidemiology and Community Medicine, Faculty of Medicine, University of Ottawa [Y. C., W. T.], and Cancer Bureau, Laboratory Centre for Disease Control, Health Canada, Ottawa, Ontario, Canada K1H 8M5 [R. S., Y. M.]


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Occurrence
 Risk Factors
 Second Malignancies of Other...
 Implications for Future Studies
 References
 
Two to 11% of women diagnosed with breast cancer will develop contralateral breast cancer in their lifetime. Women with a first primary are at a 2–6-fold increased risk of developing contralateral breast cancer compared with the risk in the general population of women developing a first primary cancer. The incidence rate of contralateral breast cancer varies from four to eight per 1000 person-years. To assess the risk factors associated with the development of contralateral breast cancer among women with a first primary breast cancer, the epidemiological literature concerning these factors was reviewed and summarized. Studies have shown that a family history of breast cancer, an early age at initial diagnosis, and a lobular histology of the first primary breast cancer increase the risk of developing contralateral breast cancer. Although chemotherapy and tamoxifen therapy may reduce this risk, there are inconsistent results regarding the effects of radiotherapy and the effects of reproductive, environmental and other factors. Additional analytical studies addressing all potential risk factors associated with the development of contralateral breast cancer are necessary in view of the increasing incidence and survival of women with a first primary.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Occurrence
 Risk Factors
 Second Malignancies of Other...
 Implications for Future Studies
 References
 
The study of contralateral breast cancer is becoming an important public health issue because of the increased incidence of first primary breast cancer and improved survival (1) . The first description of contralateral breast cancer was published in 1921 (2) . Contralateral breast cancer is of etiological interest because there may be shared risk factors between the first and second primaries (e.g., a family history of breast cancer), whereas other risk factors can be unique to the second primary (e.g., radiotherapy). Understanding the etiology of contralateral breast cancer should help identify patients who are at an increased risk and alleviate some of the ambiguity surrounding the involvement of environmental, genetic, and hormonal factors influencing the development of breast cancer (3 , 4) . It should also help monitor the effects of treatment of the first primary breast cancer, especially radiotherapy and chemotherapy.

The objective of this report is to provide an overview of the frequency of contralateral breast cancer and summarize the potential risk factors associated with the development of a second primary breast cancer. The ability to identify which patients are at an increased risk of developing contralateral breast cancer will help both patients and physicians in determining appropriate preventive and protective methods.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Occurrence
 Risk Factors
 Second Malignancies of Other...
 Implications for Future Studies
 References
 
We undertook a MEDLINE search to find epidemiological studies, including clinical trials, which examined the frequency of a second primary breast cancer and risk factors related to the development of the disease. The reference lists from retrieved studies were manually searched to find additional studies. We also reviewed the recent issues of the major medical journals to find the most recent publications. The articles reviewed and summarized in this report were chosen based on their design, evidence of shared risk factors and treatment effects, and relevance and significance to the etiological understanding of contralateral breast cancer.

Diagnostic criteria for contralateral breast cancer have been characterized (5, 6, 7) . These criteria offer guidelines to differentiate the diagnosis of a second primary from a metastatic spread of the first primary. Epidemiological studies of contralateral breast cancer differ in the extent to which these criteria are followed. Some studies have included all women with contralateral lesions, whereas others have excluded women with contralateral lesions diagnosed within certain time intervals, e.g., 6 months, 1 year, or even longer. Women with first primary in situ lesions may have been either included or excluded. The definition and inclusion of synchronous cancers also vary widely among studies. Lack of universal criteria for a contralateral breast cancer limits the estimation of its frequency and comparison of the available studies.

Available research on contralateral breast cancer is limited by methodological design that complicates the interpretation of results from individual studies and comparisons between studies. Some epidemiological studies report findings qualitatively rather than quantitatively. There is often no comparison performed between a reference group, women with unilateral breast cancer, and the case group, women with contralateral breast cancer. This creates difficulty in determining case status and survival and ultimately the percentage of women at risk (2) . We do not use quantitative approaches, e.g., meta-analysis, to combine the results of the studies. Biases can be easily introduced in meta-analysis in such cases because of those study limitations indicated above.


   Occurrence
Top
 Abstract
 Introduction
 Materials and Methods
 Occurrence
Risk Factors
 Second Malignancies of Other...
 Implications for Future Studies
 References
 
Most investigations of the frequency of contralateral breast cancer frequency have been based upon population-based cancer registries, and others, by selected study groups. The degree of completeness of registration is an important factor affecting the accuracy of the frequency estimation, whereas selection bias may limit the interpretation of the non-population-based data. Definitive diagnosis of contralateral breast cancer is also an area of uncertainty, as indicated above. These difficulties may result in biases in the frequency estimation, which are difficult to assess.

Sixteen cohort studies were identified (Table 1)Citation . The incidence rate ranged from 3.8 to 8.0 per 1000 person-years in patients with a first primary breast cancer. The standardized incidence ratios calculated for nine of these studies ranged from 1.4 to 5.0. The cumulative incidence is affected by the length of follow-up period, ranging from 2 to 11% (5 , 10 , 23, 24, 25, 26) . Attempts to make a comparison of the incidence rates between studies may not be realistic because of previously mentioned methodological difficulties and lack of consistency.


View this table:
[in this window]
[in a new window]
  		Table 1 Incidence rate (IR) and SIR of contralateral breast cancer among women with a first primary breast cancer based on cohort data

 
The risk for women with unilateral breast cancer of developing a second primary is 2–6 times the risk in the general population of developing an initial breast cancer (12) . Most studies have shown a SIR3 of three to four (Table 1)Citation . Volk and Pompe-Kirn (22) presented a much lower SIR (1.4) compared with other studies, possibly because of misclassification of the disease. Schottenfeld (7) cautioned that the diagnosis of a second primary cancer may be subject to lead-time bias because cancer patients are under closer medical surveillance than the general population, which may result in an inflated SIR.


   Risk Factors
Top
 Abstract
 Introduction
 Materials and Methods
 Occurrence
 Risk Factors
Second Malignancies of Other...
 Implications for Future Studies
 References
 
Family History
Some studies have demonstrated that a family history of breast cancer is associated with increased risk of contralateral breast cancer (Table 2)Citation . The effect of a family history was particularly noted among women with an affected first-degree relative. Studies found that having a sister with breast cancer incurred a greater risk of contralateral breast cancer than having a mother with breast cancer (3 , 26 , 28 , 31) . However, this could be reversed among older women (31) . Cook et al. (26) showed an odds ratio of 5.27 when both mother and sister were affected; however, the 95% CI was wide (0.97–28.8) because of the small number of subjects. Women with a mother who had bilateral breast cancer and with a sister or mother with younger age at onset were at a particularly elevated risk of contralateral breast cancer (28) .


View this table:
[in this window]
[in a new window]
  		Table 2 Family history of breast cancer and contralateral breast cancer (CBC) after a first primary breast cancer in women

 
There is some evidence of a relationship between the risk of contralateral breast cancer and time since initial cancer diagnosis. The increased risk of contralateral breast cancer associated with a family history of breast cancer was greater for those with a time interval between the first and second primaries, which exceeded 1 year compared with a time interval of <1 year (15) . The risk of second primary breast cancer increased with increasing time since initial cancer diagnosis (3) . Other studies, however, found an elevated risk in the first year after initial diagnosis (10 , 12 , 32) .

A family history of other types of cancer, e.g., endometrial cancer and ovarian cancer, may also increase the risk of developing a second primary breast cancer (3 , 28) . Bernstein et al. (28) reported a relative risk of 2.13 (95% CI, 1.04–4.35) for women with a first-degree relative with endometrial cancer and a relative risk of 1.69 (95% CI, 0.42–6.83) for women with a family history of ovarian cancer.

Age at Diagnosis of the First Primary Breast Cancer
A number of studies have found that age at time of first diagnosis is the most important predictor for contralateral breast cancer. The earlier a woman develops an initial breast cancer in her lifetime, the greater the risk of developing a second primary (Table 3)Citation . The risk of a contralateral breast cancer showed an exponential decrease with increasing age at diagnosis of first primary, which might due to rapid exhaustion of a susceptible subpopulation (10) . Hankey et al. (12) found that the incidence density of bilateral breast cancer was 1,005 per 100,000 person-years in the <45 age group, 811 in the 45–54 age group, and 758 in the >=55 age group during the study period from 1960 through 1975. When age was analyzed by decade, the relative risk for older patients compared with younger patients was 0.79 (95% CI, 0.62–1.10; Ref. 21 ). A decreased risk with increasing age might be due to a longer life expectancy in younger women (34) and/or be explained by the fact that patients having a family history of breast cancer develop their cancer at an early age (18) .


View this table:
[in this window]
[in a new window]
  		Table 3 Age at diagnosis of first primary breast cancer and contralateral breast cancer (CBC) in women

 
Lobular-type History of the First Primary Breast Cancer
An increased risk of contralateral breast cancer is associated with a first primary breast cancer of lobular histology (Table 4)Citation . This may reflect fundamental differences in the biological behavior and/or etiology of tumors having their origin in cells differentiating into lobular rather than ductal cells (32) . Dixon et al. (38) and Horn and Thompson (36) found that a lobular component of the initial breast cancer, regardless of whether it was invasive or in situ, was associated with an almost 2-fold increased risk of developing a contralateral breast cancer, after adjustment for potential confounders. Fisher et al. (24) found that invasive lobular histological type was significantly associated with increased risk of contralateral breast cancer, whereas the number of in situ cases was small. Hislop et al. (15) found that lobular carcinoma of the first primary was associated with an increased risk of contralateral breast cancer only among the synchronous cases (a time interval between the first and second primaries <1 year) but not among the asynchronous cases. Habel et al. (39) studied 2211 women with a primary in situ breast cancer and found that the risk was only slightly higher for women with a first primary lobular carcinoma than for women with a first primary ductal carcinoma. There was a markedly elevated risk of contralateral ductal breast cancer, which may result from increased medical surveillance of women diagnosed with breast cancer, especially during the first year after diagnosis (39) .


View this table:
[in this window]
[in a new window]
  		Table 4 Lobular histology of the first primary breast cancer and contralateral breast cancer among women

 
Treatment of the First Primary Breast Cancer
Radiotherapy.
Most studies have documented no significant increased risk of contralateral breast cancer after radiation treatment for the initial breast cancer (12 , 13 , 23 , 30 , 32 , 36 , 37 , 40, 41, 42, 43) . Storm et al. (30) found no evidence that risk varied with radiation dose, time since exposure, or age at exposure. However, Harvey and Brinton (16) examined the data for 41,109 women diagnosed with breast cancer between 1935 and 1982 and found that women treated with radiation were at a higher risk of developing a second breast cancer than were nonirradiated women (SIR, 3.9 versus 2.8). This slight increase was also observed in a case-control study (odds ratio, 1.31; 95% CI, 0.74–1.46; Ref. 26 ). Murakami et al. (18) observed an excess risk of contralateral breast cancer in the radiotherapy group only among those diagnosed at 10 or more years after the first breast cancer diagnosis (SIR, 7.6) compared with the nonradiotherapy group (SIR, 2.9), whereas the overall SIR was 3.8 for the radiotherapy group and 4.8 for the nonradiotherapy group. Boice et al. (29) found an increased risk associated with radiotherapy only among women <45 years of age but not among older women. However, Storm and Jensen (17) studied 56,237 women with a first primary breast cancer in Denmark and found that the association between radiation and contralateral breast cancer was obvious for all ages combined but was less obvious among premenopausal (age, <45 years) and perimenopausal (age, 45–54 years) women with primary breast cancer.

Chemotherapy.
A number of studies have documented that women who received chemotherapy for the initial breast cancer showed a reduction in risk of developing a contralateral breast cancer (26 , 36 , 37 , 43, 44, 45, 46) . In a study of 292 cases with an incident contralateral breast cancer and 264 controls who survived unilateral breast cancer, Horn and Thompson (36) estimated an odds ratio of 0.3 (95% CI, 0.1–0.7) for chemotherapy treatment. A cohort study of 4660 women diagnosed with a first primary breast cancer reported by Bernstein et al. (37) showed similar results, that treatment with chemotherapy for the first primary was associated with a lower risk of developing a second breast cancer (relative risk, 0.56; 95% CI, 0.33–0.96). Chemotherapy in early breast cancer may reduce the overall risk of new primary tumors (45 , 46) . The association with chemotherapy may be modified by body build. Receiving chemotherapy was found to be protective among women of normal or reduced body weight but was associated with an increased risk among overweight women (36 , 44) .

Tamoxifen.
Most clinical trials in the past decade have documented a beneficial effect on the development of secondary breast cancer (Table 5)Citation . In a randomized, double-blinded, and placebo-controlled trial of postoperative therapy with tamoxifen in 2644 women with breast cancer, Fisher et al. (42) found that the tamoxifen group demonstrated a significant reduction of contralateral breast cancer than the placebo group. On the basis of the data from 75,000 women in 133 randomized trials, a meta-analysis conducted by the Early Breast Cancer Trialists’ Collaborative Group (46) showed a reduction of 39% in the risk of development of contralateral breast cancer. Rutqvist et al. (47) provided a similar estimation for reduction of contralateral breast cancer with tamoxifen therapy, based on the data from 1846 postmenopausal breast cancer women, and found that the benefit with tamoxifen therapy was greatest during the first 2 years. The studies by the Scottish Cancer Trials Breast Group (48) and the Cancer Research Campaign Breast Cancer Trials Group (49) also found overall beneficial effects of adjuvant tamoxifen on the incidence of contralateral breast cancer. The odds ratio for tamoxifen therapy associated with contralateral breast cancer ranges from 0.5 to 0.6 in both clinical and population studies (50, 51, 52) . The beneficial effect of tamoxifen therapy may be dependent on menopausal status and disease status. One study performed a subgroup analysis according to menopausal status and found a reduction in the risk of contralateral breast cancer for postmenopausal women and a marginal increase in risk for premenopausal women (49) . In a study of 3538 postmenopausal patients who had received surgical treatment for primary breast cancer, Andersson et al. (53) found a similar incidence rate of contralateral breast cancer in the high-risk tamoxifen-treated group and in the high-risk group not treated with tamoxifen.


View this table:
[in this window]
[in a new window]
  		Table 5 Clinical trials of Tamoxifen therapy treatment and contralateral breast cancer among women

 
Reproductive Factors
Some studies have shown that a later age at the birth of the first child is associated with an increase in risk of contralateral breast cancer (13 , 15 , 54) ; however, other studies have suggested that it may protect against development of contralateral breast cancer (3 , 27 , 55) . A longer interval between menarche and the birth of the first child may be a risk factor for the contralateral breast cancer (13) . Cook et al. (26) found little variation related to menopausal status, except that women who were postmenopausal because of bilateral oophorectomy at initial breast cancer diagnosis had a reduction in the risk of contralateral breast cancer compared with premenopausal women (odds ratio, 0.25; 95% CI, 0.09–0.68). Bernstein et al. (37) found a negative association with the number of third trimester pregnancies. Most studies found no relationship between nulliparity and contralateral breast cancer (3 , 15 , 29 , 37 , 54) , except the one by Sakamoto et al. (56) . Some studies showed slight protective effects of multiple births on the development of contralateral breast cancer (27 , 30 , 37 , 54) , whereas others did not (3 , 13 , 15) .

Body Weight
Kato et al. (27) reported a 3-fold increased risk of second primary cancer among women who weighed more than 60 kg compared with those having a body weight of 60 kg or less. Storm et al. (30) found that the relative risk was 1.37 (95% CI, 0.94–2.00) for the 25–29 kg/m2 group and 1.77 (95% CI, 1.00–3.14) for the 30+ kg/m2 group versus the <25 kg/m2 group. However, other studies showed no increased risk for contralateral breast cancer in relation to being overweight (3 , 15 , 37) .

Other Factors
An increased risk was observed by Bernstein et al. (37) among women who had reported a personal history of benign breast disease before their first primary breast cancer (rate ratio, 1.69; 95% CI, 1.13–2.53) and by Horn and Thompson (Ref. 3 ; odds ratio, 1.4; 95% CI, 0.7–2.7), whereas two earlier studies showed no clear association between a benign breast disease history and contralateral breast cancer (13 , 27) .

Having never married was protective in young women, but the opposite was found among older women (32) . A positive progesterone receptor assay and AB blood type were associated with an elevated risk of contralateral breast cancer (3) .

Bernstein et al. (37) observed no increased risk of contralateral breast cancer in relation to alcohol consumption and cigarette smoking, but Kato et al. (27) and Horn and Thompson (3) found somewhat detrimental effects of alcohol and smoking, respectively, on contralateral breast cancer. The use of oral contraceptives was not associated with contralateral breast cancer (3 , 13 , 15 , 37) .


   Second Malignancies of Other Organs
Top
 Abstract
 Introduction
 Materials and Methods
 Occurrence
 Risk Factors
 Second Malignancies of Other...
Implications for Future Studies
 References
 
Women with breast cancer are at an increased risk of developing second primary cancers, not only of the breast but also of other organs. Studies of multiple primary cancers have indicated that for women with breast carcinomas, there is an excess risk for cancers of the colon, ovary, thyroid, and corpus uteri and for malignant melanoma (16 , 22 , 57) . Although these results are not entirely consistent for all studies, the development of a second primary cancer may suggest common risk factors related to the first primary.

Possible factors used to explain the association of multiple primary cancers include genetic influences, endogenous hormones, common environmental exposures, and treatment of the first primary breast cancer. These associations have generally been found to be reciprocal; for example, patients with ovarian cancer as a first primary are at an elevated risk of developing a second primary of the breast (1 , 10 , 58) .

The risks of developing leukemia, cancer of the lung and kidney, and non-Hodgkin’s lymphoma after breast cancer is increased and has primarily been attributed to the effects of treatment (1 , 16 , 58) . The importance of shared risk factors and treatment effects associated with multiple primaries has been described (4) . Results from studies of multiple primaries may lead to identifying the etiological role of certain risk factors and/or isolating potential risk factors associated with treatment modalities such as radiation and chemotherapy.


   Implications for Future Studies
Top
 Abstract
 Introduction
 Materials and Methods
 Occurrence
 Risk Factors
 Second Malignancies of Other...
 Implications for Future Studies
References
 
Research on the occurrence of second primary neoplasms can provide useful information regarding shared risk factors for the first and second neoplasms. These studies may also help monitor treatment effects of radiotherapy, chemotherapy, and tamoxifen therapy. There is no clear evidence that any of the following risk factors play a role in the development of contralateral breast cancer: age, race, reproductive variables, alcohol consumption, cigarette smoking, body weight, or use of oral contraceptives.

Treatment effects should continue to be monitored, and future guidelines should be provided for long-term surveillance of surviving cancer patients. Up-to-date and complete cancer registries would facilitate future epidemiological studies.


   Acknowledgments
 
We thank Dr. Edgar Love and Kathy Clarke for comments.


   Footnotes
 
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Supported by the Health Canada Breast Cancer Initiative. Y. C. is a National Health Research Scholar of the National Health Research and Development Program, Health Canada. Back

2 To whom requests for reprints should be addressed, at Department of Epidemiology and Community Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8M5 Canada. Phone: (613) 562-5800, extension 8287; Fax: (613) 562-5465; E-mail: chen{at}zeus.med.uottawa.ca Back

3 The abbreviations used are: SIR, standardized incidence ratio; CI, confidence interval. Back

Received 8/24/98; revised 5/28/99; accepted 6/ 7/99.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Occurrence
 Risk Factors
 Second Malignancies of Other...
 Implications for Future Studies
 References
 

  1. Horn-Ross P. L. Multiple primary cancers involving the breast. Epidemiol. Rev., 15: 169-176, 1993.[Free Full Text]
  2. Kilgore A. R. The incidence of cancer in the second breast. J. Am. Med. Assoc., 77: 454-457, 1921.
  3. Horn P. L., Thompson W. D. Risk of contralateral breast cancer: associations with factors related to initial breast cancer. Am. J. Epidemiol., 128: 309-323, 1988.[Abstract/Free Full Text]
  4. Thompson W. D. Methodologic perspectives on the study of multiple primary cancers. Yale J. Biol. Med., 59: 505-516, 1986.[Medline]
  5. Robbins G. F., Berg J. W. Bilateral primary breast cancers: a prospective clinicopathological study. Cancer (Phila.), 17: 1501-1527, 1964.[Medline]
  6. Lewison E. F., Neto A. S. Bilateral breast cancer at the Johns Hopkins Hospital: a discussion of the dilemma of contralateral breast cancer. Cancer (Phila.), 28: 1297-1301, 1971.[Medline]
  7. Schottenfeld D. Multiple primary cancers Ed. 2 Schottenfeld D. Fraumen J. F., Jr. eds. . Cancer Epidemiology and Prevention, : 1370-1381, Oxford University Press New York 1996.
  8. Haagensen C. D. Diseases of the Breast Ed. 2 449-458, W. B. Saunders Co. Philadelphia 1971.
  9. Schottenfeld D., Berg J. Incidence of multiple primary cancers. IV. Cancers of the female breast and genital organs. J. Natl. Cancer Inst., 46: 161-170, 1971.
  10. Prior P., Waterhouse J. A. H. Incidence of bilateral tumours in a population-based series of breast-cancer patients. I. Two approaches to an epidemiological analysis. Br. J. Cancer, 37: 620-634, 1978.[Medline]
  11. Mueller C. B., Ames F. Bilateral carcinoma of the breast: frequency and mortality. Can. J. Surg., 21: 459-465, 1978.[Medline]
  12. Hankey B. F., Curtis R. E., Naughton M. D., Boice J. D., Jr., Flannery J. T. A retrospective cohort analysis of second breast cancer risk for primary breast cancer patients with an assessment of the effect of radiation therapy. J. Natl. Cancer Inst., 70: 797-804, 1983.
  13. Burns P. E., Dabbs K., May C., Lees A. W., Birkett L. R., Jenkins H. J., Hanson J. Bilateral breast cancer in Northern Alberta: risk factors and survival patterns. Can. Med. Assoc. J., 130: 881-886, 1984.[Abstract]
  14. Chaudary M. A., Millis R. R., Hoskins E. O., Halder M., Bulbrook R. D., Cuzick J., Hayward J. L. Bilateral primary breast cancer: a prospective study of disease incidence. Br. J. Surg., 71: 711-714, 1984.[Medline]
  15. Hislop T. G., Elwood J. M., Coldman A. J., Spinelli J. J., Worth A. J., Ellison L. G. Second primary cancers of the breast: incidence and risk factors. Br. J. Cancer, 49: 79-85, 1984.[Medline]
  16. Harvey E. B., Brinton L. A. Second cancer following cancer of the breast in Connecticut, 1935–1982. Natl. Cancer Inst. Monogr., 68: 99-112, 1985.
  17. Storm H. H., Jensen O. M. Risk of contralateral breast cancer in Denmark, 1943–1980. Br. J. Cancer, 54: 483-492, 1986.[Medline]
  18. Murakami R., Hiyama T., Hanai A., Fujimoto I. Second primary cancers following female breast cancer in Osaka, Japan: a population-based cohort study. Jpn. J. Clin. Oncol., 17: 293-302, 1987.[Abstract/Free Full Text]
  19. Rosen P. P., Groshen S., Kinne D. W., Hellman S. Contralateral breast carcinoma: an assessment of risk and prognosis in Stage I (T1N0M0) and Stage II (T1N1M0) patients with 20-year follow-up. Surgery, 106: 904-910, 1989.[Medline]
  20. Brenner H., Siegle S., Stegmaier C., Ziegler H. Second primary neoplasms following breast cancer in Saarland, Germany, 1968–1987. Eur. J. Cancer, 29A: 1410-1414, 1993.
  21. Healey E. A., Cook E. F., Orav E. J., Schnitt S. J., Connolly J. L., Harris J. R. Contralateral breast cancer: clinical characteristics and impact on prognosis. J. Clin. Oncol., 11: 1545-1552, 1993.[Abstract/Free Full Text]
  22. Volk N., Pompe-Kirn V. Second primary cancers in breast cancer patients in Slovenia. Cancer Causes Control, 8: 764-770, 1997.[Medline]
  23. McCredie J. A., Inch W. R., Alderson M. Consecutive primary carcinomas of the breast. Cancer (Phila.), 35: 1472-1477, 1975.[Medline]
  24. Fisher E. R., Fisher B., Sass R., Wickerham L., Collaborating NSABP Investigators Pathologic findings from the National Surgical Adjuvant Breast Project (Protocol No. 4). XI. Bilateral breast cancer. Cancer (Phila.), 54: 3002-3011, 1984.[Medline]
  25. Kurtz J. M., Amalric R., Brandone H., Ayme Y., Spitalier J-M. Contralateral breast cancer and other second malignancies in patients treated by breast-conserving therapy with radiation. Int. J. Radiat. Oncol. Biol. Phys., 15: 277-284, 1988.[Medline]
  26. Cook L. S., White E., Schwartz S. M., McKnight B., Daling J. R., Weiss N. S. A population-based study of contralateral breast cancer following a first primary breast cancer (Washington, United States). Cancer Causes Control, 7: 382-390, 1996.[Medline]
  27. Kato I., Miura S., Yoshida M., Tominaga S. Risk factors of multiple primary cancers in breast cancer patients. Jpn. J. Cancer Res., 77: 296-304, 1986.[Medline]
  28. Bernstein J. L., Thompson W. D., Risch N., Holford T. R. The genetic epidemiology of second primary breast cancer. Am. J. Epidemiol., 136: 937-948, 1992.[Abstract/Free Full Text]
  29. Boice J. D., Jr., Harvey E. B., Blettner M., Stovall M., Flannery J. T. Cancer in the contralateral breast after radiotherapy for breast cancer. N. Engl. J. Med., 326: 781-785, 1992.[Abstract]
  30. Storm H. H., Andersson M., Boice J. D., Jr., Blettner M., Stovall M., Mouridsen H. T., Dombernowsky P., Rose C., Jacobsen A., Pedersen M. Adjuvant radiotherapy and risk of contralateral breast cancer. J. Natl. Cancer Inst., 84: 1245-1250, 1992.[Abstract/Free Full Text]
  31. Anderson D. E., Badzioch M. D. Bilaterality in familial breast cancer patients. Cancer (Phila.), 56: 2092-2098, 1985.[Medline]
  32. Horn P. L., Thompson W. D., Schwartz S. M. Factors associated with the risk of second primary breast cancer: an analysis of data from the Connecticut Tumor Registry. J. Chronic Dis., 40: 1003-1011, 1987.[Medline]
  33. Broet P., de la Rochefordiere A., Scholl S. M., Fourquet A., Mosseri V., Durand J-C., Pouillart P., Asselain B. Contralateral breast cancer: annual incidence and risk parameters. J. Clin. Oncol., 13: 1578-1583, 1995.[Abstract/Free Full Text]
  34. Adami H-O., Hansen J., Jung B., Lindgren A., Rimsten A. Bilateral carcinoma of the breast: epidemiology and histopathology. Acta. Radiol. Oncol., 20: 305-309, 1981.[Medline]
  35. Webber B. L., Heise H., Neifeld J. P., Costa J. Risk of subsequent contralateral breast carcinoma in a population of patients with in-situ breast carcinoma. Cancer (Phila.), 47: 2928-2932, 1981.[Medline]
  36. Horn P. L., Thompson W. D. Risk of contralateral breast cancer: associations with histologic, clinical and therapeutic factors. Cancer (Phila.), 62: 412-424, 1988.[Medline]
  37. Bernstein J. L., Thompson W. D., Risch N., Holford T. R. Risk factors predicting the incidence of second primary breast cancer among women diagnosed with a first primary breast cancer. Am. J. Epidemiol., 136: 925-936, 1992.[Abstract/Free Full Text]
  38. Dixon J. M., Anderson T. J., Page D. L., Lee D., Duff S. W., Stewart H. J. Infiltrating lobular carcinoma of the breast: an evaluation of the incidence and consequence of bilateral disease. Br. J. Surg., 70: 513-516, 1983.[Medline]
  39. Habel L. A., Moe R. E., Daling J. R., Holte S., Rossing M. A., Weiss N. S. Risk of contralateral breast cancer among women with carcinoma in situ of the breast. Ann. Surg., 225: 69-75, 1997.[Medline]
  40. Basco V. E., Coldman A. J., Elwood J. M., Young M. E. J. Radiation dose and second breast cancer. Br. J. Cancer, 52: 319-325, 1985.[Medline]
  41. Parker R. G., Grimm P., Enstrom J. E. Contralateral breast cancers following treatment for initial breast cancers in women. Am. J. Clin. Oncol., 12: 213-216, 1989.[Medline]
  42. Fisher B., Costantino J., Redmond C., Poisson R., Bowman D., Couture J., Dimitrov N. V., Wolmark N., Wickerham D. L., Fisher E. R., Margolese R., Robidoux A., Shibata H., Terz J., Paterson A. H. G., Feldman M. I., Farrar W., Evans J., Lickley H. L., Ketner M., et al A randomized clinical trial evaluating Tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. N. Engl. J. Med., 320: 479-484, 1989.[Abstract]
  43. Lavey R. S., Eby N. L., Prosnitz L. R. Impact of radiation therapy and/or chemotherapy on the risk for a second malignancy after breast cancer. Cancer (Phila.), 66: 874-881, 1990.[Medline]
  44. Horn P. L., Thompson W. D. Exposure to chemotherapeutic agents and the risk of a second breast cancer: preliminary findings. Yale J. Biol. Med., 61: 223-231, 1988.[Medline]
  45. Arriagada R., Rutqvist L. E. Adjuvant chemotherapy in early breast cancer and incidence of new primary malignancies. Lancet, 338: 535-538, 1991.[Medline]
  46. Early Breast Cancer Trialists’ Collaborative Group Systemic treatment of early breast cancer by hormonal, cytotoxic or immune therapy. Lancet, 339: 1–15-7185, 1992.[Medline]
  47. Rutqvist L. E., Cedermark B., Glas U., Mattsson A., Skoog L., Somell A., Theve T., Wilking N., Askergren J., Hjalmar M-L., Rotstein S., Perbeck L., Ringborg U. Contralateral primary tumors in breast cancer patients in a randomized trial of adjuvant tamoxifen therapy. J. Natl. Cancer Inst., 83: 1299-1306, 1991.[Abstract/Free Full Text]
  48. Stewart H. J. The Scottish trial of adjuvant tamoxifen in node-negative breast cancer. J. Natl. Cancer Inst. Monogr., 11: 117-120, 1992.
  49. Cancer Research Campaign Breast Cancer Trials Group The effect of adjuvant tamoxifen: the latest results from the Cancer Research Campaign Adjuvant Breast Trial. Eur. J. Cancer, 28A: 904-907, 1992.
  50. Fornander T., Rutqvist L. E., Cedermark B., Glas U., Mattsson A., Silfversward C., Skoog L., Somell A., Theve T., Wilking N., Askergren J., Hjalmar M-L. Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers. Lancet, 1: 117-120, 1989.[Medline]
  51. Rutqvist L. E., Johansson H., Signomklao T., Johansson U., Fornander T., Wilking N. Adjuvant tamoxifen therapy for early-stage breast cancer and second primary malignancies. Stockholm Breast Cancer Study Group. J. Natl. Cancer. Inst., 87: 645-651, 1995.[Abstract/Free Full Text]
  52. Cook L. S., Weiss N. S., Schwartz S. M., White E., McKnight B., Moore D. E., Daling J. R. Population-based study of tamoxifen therapy and subsequent ovarian, endometrial and breast cancers. J. Natl. Cancer. Inst., 87: 1359-1364, 1995.[Abstract/Free Full Text]
  53. Andersson M., Storm H. H., Mouridsen H. T. Incidence of new primary cancers after adjuvant tamoxifen therapy and radiotherapy for early breast cancer. J. Natl. Cancer Inst., 83: 1013-1017, 1991.[Abstract/Free Full Text]
  54. Adami H-O., Bergstrom R., Hansen J. Age at first primary as a determinant of the incidence of bilateral breast cancer: cumulative and relative risks in a population-based case-control study. Cancer (Phila.), 55: 643-647, 1985.[Medline]
  55. Haagensen C. D., Bodian C., Haagensen D. E. Breast Carcinoma: Risk and Detection339-364, W. B. Saunders Co. Philadelphia 1981.
  56. Sakamoto G., Sugano H., Kasumi F. Bilateral breast cancer and familial aggregations. Prev. Med., 7: 225-229, 1978.[Medline]
  57. Schwartz A. G., Ragheb N. E., Swanson G. M. Race and age differences in multiple primary cancers after breast cancer: a population-based analysis. Breast Cancer Res. Treat., 14: 245-254, 1989.[Medline]
  58. Boice, J. D., Jr., Connecticut Tumor Registry, and Cancerregisteret (Denmark) (eds). Multiple Primary Cancers in Connecticut and Denmark. National Cancer Institute Monograph Number 68. NIH Publication Number 85-2714. Bethesda, MD: National Cancer Institute, 1985.



This article has been cited by other articles:


Home page
 JNCI J Natl Cancer InstHome page
L. Bertelsen, L. Bernstein, J. H. Olsen, L. Mellemkjaer, R. W. Haile, C. F. Lynch, K. E. Malone, H. Anton-Culver, J. Christensen, B. Langholz, et al.
Effect of Systemic Adjuvant Treatment on Risk for Contralateral Breast Cancer in the Women's Environment, Cancer and Radiation Epidemiology Study
J Natl Cancer Inst, January 2, 2008; 100(1): 32 - 40.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. Hartman, K. Czene, M. Reilly, J. Adolfsson, J. Bergh, H.-O. Adami, P. W. Dickman, and P. Hall
Incidence and Prognosis of Synchronous and Metachronous Bilateral Breast Cancer
J. Clin. Oncol., September 20, 2007; 25(27): 4210 - 4216.
[Abstract] [Full Text] [PDF]

Home page
 RadiologyHome page
F. Pediconi, C. Catalano, A. Roselli, S. Padula, F. Altomari, E. Moriconi, A. M. Pronio, M. A. Kirchin, and R. Passariello
Contrast-enhanced MR Mammography for Evaluation of the Contralateral Breast in Patients with Diagnosed Unilateral Breast Cancer or High-Risk Lesions
Radiology, June 1, 2007; 243(3): 670 - 680.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
J. A. Largent, M. Capanu, L. Bernstein, B. Langholz, L. Mellemkjaer, K. E. Malone, C. B. Begg, R. W. Haile, C. F. Lynch, H. Anton-Culver, et al.
Reproductive History and Risk of Second Primary Breast Cancer: The WECARE Study
Cancer Epidemiol. Biomarkers Prev., May 1, 2007; 16(5): 906 - 911.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. Hemminki, J. Ji, and A. Forsti
Risks for Familial and Contralateral Breast Cancer Interact Multiplicatively and Cause a High Risk
Cancer Res., February 1, 2007; 67(3): 868 - 870.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. J. Kelloff, S. M. Lippman, A. J. Dannenberg, C. C. Sigman, H. L. Pearce, B. J. Reid, E. Szabo, V. C. Jordan, M. R. Spitz, G. B. Mills, et al.
Progress in Chemoprevention Drug Development: The Promise of Molecular Biomarkers for Prevention of Intraepithelial Neoplasia and Cancer--A Plan to Move Forward
Clin. Cancer Res., June 15, 2006; 12(12): 3661 - 3697.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. Bonneterre, H. Roche, P. Kerbrat, A. Bremond, P. Fumoleau, M. Namer, M.-J. Goudier, S. Schraub, P. Fargeot, and I. Chapelle-Marcillac
Epirubicin Increases Long-Term Survival in Adjuvant Chemotherapy of Patients With Poor-Prognosis, Node-Positive, Early Breast Cancer: 10-Year Follow-Up Results of the French Adjuvant Study Group 05 Randomized Trial
J. Clin. Oncol., April 20, 2005; 23(12): 2686 - 2693.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
W. McCaskill-Stevens, J. Wilson, J. Bryant, E. Mamounas, L. Garvey, J. James, W. Cronin, and D. L. Wickerham
Contralateral Breast Cancer and Thromboembolic Events in African American Women Treated With Tamoxifen
J Natl Cancer Inst, December 1, 2004; 96(23): 1762 - 1769.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
M. D. Schwartz, C. Lerman, B. Brogan, B. N. Peshkin, C. Hughes Halbert, T. DeMarco, W. Lawrence, D. Main, C. Finch, C. Magnant, et al.
Impact of BRCA1/BRCA2 Counseling and Testing on Newly Diagnosed Breast Cancer Patients
J. Clin. Oncol., May 15, 2004; 22(10): 1823 - 1829.
[Abstract] [Full Text] [PDF]

Home page
 Arch SurgHome page
J. N. Weitzel, S. M. McCaffrey, R. Nedelcu, D. J. MacDonald, K. R. Blazer, and C. A. Cullinane
Effect of Genetic Cancer Risk Assessment on Surgical Decisions at Breast Cancer Diagnosis
Arch Surg, December 1, 2003; 138(12): 1323 - 1328.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
T. Bachleitner-Hofmann, B. Pichler-Gebhard, M. Rudas, M. Gnant, S. Taucher, D. Kandioler, E. Janschek, P. Dubsky, S. Roka, E. Sporn, et al.
Pattern of Hormone Receptor Status of Secondary Contralateral Breast Cancers in Patients Receiving Adjuvant Tamoxifen
Clin. Cancer Res., November 1, 2002; 8(11): 3427 - 3432.
[Abstract] [Full Text] [PDF]

Home page
 JNCI J Natl Cancer InstHome page
C. I. Li, K. E. Malone, N. S. Weiss, and J. R. Daling
Tamoxifen Therapy for Primary Breast Cancer and Risk of Contralateral Breast Cancer
J Natl Cancer Inst, July 4, 2001; 93(13): 1008 - 1013.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chen, Y.
Right arrow Articles by Mao, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, Y.
Right arrow Articles by Mao, Y.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Cell Growth & Differentiation