Journal of the National Cancer Institute Advance Access originally published online on June 27, 2007
JNCI Journal of the National Cancer Institute 2007 99(13):1044-1049; doi:10.1093/jnci/djm026
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
BRIEF COMMUNICATION |
Rising Incidence Rates of Breast Carcinoma With Micrometastatic Lymph Node Involvement
Affiliations of authors: Surveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD (DPCF, LAR, BKE); Department of Clinical Epidemiology, Aarhus University Hospital, Denmark (DPCF); Office of Healthcare Inspections, Office of Inspector General, U.S. Department of Veterans Affairs, Washington, DC (LXE)
Correspondence to: Deirdre P. Cronin-Fenton, PhD, Department of Clinical Epidemiology, Aarhus University Hospital, Ole Worms Alle 1150, 8000 Aarhus C, Denmark (e-mail: dc{at}dce.au.dk).
 |
ABSTRACT |
|---|
 Top Abstract Context and CaveatsFundingReferencesNotes |
|---|
We investigated the increased incidence of early-stage breast cancer with micrometastatic lymph node involvement. Breast cancer incidence trends from 1990 through 2002 in the US Surveillance, Epidemiology, and End Results Program catchment area were analyzed. Joinpoint regression was used to show the annual percentage change (APC) in breast cancer incidence trends. The overall incidence of breast cancer among women aged 50–64 years increased 1.8% (95% confidence interval [CI] = 1.4% to 2.2%) per annum from 1990 through 2002 but decreased in all other age groups. Stage IIA and stage IIB tumor incidence increased (APC for stage IIA from 1996 to 2002 = 61.9%, 95% CI = 51.1% to 73.4%, and APC for stage IIB from 1998 to 2002 = 53.7%, 95% CI = 20.6% to 96.0%). The incidence of micrometastatic lymph node involvement for stage IIA and stage IIB tumors increased during the 1990s, especially after 1997 (APC = 17.3% for both stages), more for estrogen receptor–positive than estrogen receptor–negative disease. Increased use of mammography screening partly explains the increased incidence of early-stage breast cancer. Increases in small tumors with micrometastatic lymph node involvement may be attributable to the increased use of the sentinel lymph node biopsy in community practice.
Prior knowledge The effect of the recent increase in the use of sentinel lymph node biopsy on the incidence of breast cancer with micrometastatic lymph node involvement was unknown. Study design Regression analysis was used to identify trends in the incidence of breast cancer according to stage and lymph node involvement based on data from the Surveillance, Epidemiology, and End Results Program. Contribution Increases in the incidence of breast cancer with micrometastatic lymph node involvement were identified that were consistent with an effect of increased detection due to more widespread use of sentinel lymph node biopsy in recent years. Implications The results of this study predict that as the use of sentinel lymph node biopsy continues to increase, the incidence of breast cancer with lymph node metastases will increase in parallel. Limitations The study was conducted without the knowledge as to which patients underwent sentinel lymph node biopsy and without the information on trends in the use of the procedure that would be needed for a more conclusive assessment of the effects of sentinel lymph node biopsy on breast cancer diagnosis.
|
Population-based mammographic screening has contributed to the increased detection of small (<2 cm), early-stage tumors (1–4). In addition, in the United States, increased incidence of tumors larger than 2 cm has been noted and attributed to changes in reproductive patterns and increased use of population-based mammography (4). Although mammography is likely to have contributed to the increased incidence of small, localized tumors, it may not be solely responsible for the increased incidence of regional disease, which can include larger tumors with lymph node metastases and tumor extension beyond the primary site. The increase in regional disease may therefore be also due to the introduction of the sentinel lymph node biopsy (SLNB) (5–7).
The sentinel node is the primary drainage destination of any metastasizing tumor cells (8,9) and can be identified using either a blue dye, a radiolabeled colloid, or a combination of the two (10,11). Research indicates that there can be more than one sentinel node per tumor (47). SLNB involves meticulous pathological examination, which can lead to upstaging of disease (12). Although it is considered to be a potentially important experimental tool for identifying occult lymph node metastases (13,14), SLNB is not recommended for routine clinical use (15–17). Evidence suggests, however, that SLNB has been incorporated into national practice (18–21). Its effectiveness at distinguishing micro- from macrometastatic disease remains controversial, and its false-negative rate of 0%–15% necessitates additional axillary lymph node dissection (ALND) (6,15,22,23).
Our US population–based study focused on the increased incidence of stage IIA and stage IIB disease with micrometastatic lymph node involvement. Stage IIA disease is defined as no tumor or tumor less than 2 cm with one to three positive lymph nodes, or tumor 2–5 cm in diameter without evidence of disease in axillary lymph nodes. Stage IIB disease is defined as tumor 2–5 cm in diameter with one to three positive lymph nodes, or tumor larger than 5 cm without any disease in the chest wall or lymph nodes. For both stage IIA and IIB, disease can be identified as microscopic disease using SLNB (48). We hypothesized that the increase is attributable to the increased use of SLNB in clinical practice. We used joinpoint regression to estimate the annual percentage change (APC) in breast cancer incidence rates, stratifying our analyses at the approximate time that the SLNB was introduced in the United States to assess its impact on the incidence of micrometastatic disease.
Information on women with a first primary breast cancer in 1990 through 2002 was obtained from cancer registries in the US National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registries (Connecticut, Iowa, New Mexico, Hawaii, Atlanta, Detroit, San Francisco-Oakland, Seattle-Puget Sound, and Utah). Breast cancers were staged using the American Joint Committee on Cancer staging system (AJCC, 3rd edition). Micrometastatic disease was defined as metastatic foci of less than 2 mm in diameter in the lymph nodes (24,25).
Analyses were performed using the SEER-Stat program, version 6.1.4 (available at http://seer.cancer.gov/seerstat/). Incidence rates per 100000 were age adjusted to the 2000 US standard (http://seer.cancer.gov/stdpopulations/single_age.html). Breast cancer incidence trends were analyzed by joinpoint regression analysis, which estimates the APC in rates by selecting the best fitting regression line segment. Joinpoint selects time periods within an overall time frame so that the incidence trend is as uniform as possible within each selected time period (26). Three joinpoints, each denoting a statistically significant change in trend, were allowed for each model. Incidence trends were based on observed data and are not adjusted for reporting delay (27).
During the 1980s, stage II node-positive breast cancer incidence declined due to the detection of small tumors using population-based mammography (49,50). By contrast, in the 1990s when that of stage II tumors with one examined lymph node increased (Table 1) (4). Stage II tumors are, by definition, small tumors (<5 cm) with evidence of disease in a maximum of three lymph nodes, or larger tumors of more than 5 cm without lymph node involvement. As Table 1 shows, our findings indicate that stage IIA tumors that were smaller than 2 cm with one examined lymph node increased 7.2% per annum (95% confidence interval [CI] = 0.1 to 14.9) from 1990 to 1996 and 61.9% per annum (95% CI = 51.1 to 73.4) from 1996 to 2002 (Table 1). Stage IIB tumors (2–5 cm with one examined lymph node) increased 10.6% per annum (95% CI = 1.7 to 20.2) from 1990 to 1998 and 53.7% per annum (95% CI = 20.6 to 96.0) from 1998 to 2002. These findings are similar to those of a Dutch population–based study, which documented increased incidence of tumors sized more than 2 cm at the advent of mammography followed by a decrease and subsequent increased incidence of node-positive tumors after the prevalent screening round, which they attributed to the introduction of SLNB (7). Our finding of an increase in stage II node-positive cancers may reflect a change in the clinical management of breast cancer, specifically the increased use of SLNB.
|
Sentinel lymph node biopsy use in academic centers is estimated to have increased from 8% in 1997 to 58% in 2000 (28), and in the SEER registries, an increased prevalence of SLNB from 1998 through 2000 of 20%–30% has been documented (21). This trend is likely to have continued in recent years. To assess the impact of the increased use of SLNB on breast cancer incidence, we stratified our analysis of the incidence of early-stage tumors categorized by size and lymph node involvement in December 1996, which is approximately the time when SLNB was introduced in the United States (28). We observed (Table 2) a substantial increase in stage IIA disease (APC [1990–1996] = 10.9%, 95% CI = 5.8 to 16.2; APC [1997–2002] = 17.3%, 95% CI = 8.0 to 27.4), and stage IIB disease (APC [1990–1996] = 17.1%, 95% CI = 11.1 to 23.4; APC [1997–2002] = 17.3%, 95% CI = 2.0 to 34.8). Although we could not determine the exact use of SLNB, our findings suggest the increased dissemination of the procedure in community clinical practice.
|
Our findings indicate an increased incidence of breast cancer with micrometastatic lymph node involvement before the introduction of SLNB (from 1990 to 1996) in routine clinical practice in the United States (about 1997) (28). This may be attributable to the increasing use of population-based mammography and a general increase in breast cancer awareness. However, the increase in micrometastatic lymph node disease in the pre-SNLB era may also reflect a gradual introduction of the technique into surgical practice. Mastery of the surgical procedure has an associated learning curve (29), and surgeons need to perform 20–30 SLNB procedures in conjunction with ALND to achieve a high rate of accuracy (30,31). Such a learning phase where SLNB is performed in conjunction with ALND has been followed by a mature phase where ALND is performed only if a positive SLNB was identified in patients (28). The increased incidence of micrometastatic lymph node disease during the 1990s may therefore be due to the combined effect of this learning curve and increased use in routine surgical practice (17).
SLNB is less invasive than ALND (32–34) and facilitates more accurate staging (6,28,35,36). Research has indicated that 25% of patients with sentinel node micrometastases had residual axillary disease (21), whereas patients with a single sentinel node micrometastasis and more than four disease-free sentinel nodes were unlikely to have axillary disease (37). It is estimated that 60%–80% of patients with small breast tumors have tumor-free sentinel nodes (35). Because ALND is associated with long-term morbidity, including lymphedema, arm pain, and upper arm paresthesia, SLNB is a more accurate and less invasive staging procedure.
SLNB, used in preference to ALND, may be the cause of a stage migratory or "Will Rogers" effect (12,36,38). For example, if SLNB reveals micrometastatic lymph node foci, stage IIA disease (T2N0—tumors sized 2–5 cm with no disease in the lymph nodes [N0]) could become stage IIB (T2N1—tumors sized 2–5 cm with one positive, micrometastatic lymph node). Thus, before the advent of SLNB, stage II node-positive breast cancers may have been considered to be stage I, node-negative disease. Our findings may reflect the impact of such upstaging on breast cancer incidence rates.
A number of distinct techniques are used to identify micrometastatic tumor cells including hematoxylin and eosin (H & E) staining, immunohistochemistry (IHC), and reverse transcription-polymerase chain reaction (RT-PCR). Schouten et al. (7) reported that, during the introduction of the SLNB technique, IHC and SLNB were used in the Netherlands to improve the accuracy of detecting lymph node metastases (7). A study by de Widt-Levert detected micrometastatic disease by IHC only, however, some IHC-positive cells in sentinel nodes can be benign epithelial cells (12). The SEER database, used in this study, includes micrometastatic disease identified by H & E staining, and not that identified by IHC or RT-PCR (April Fritz: unpublished data). H & E staining is said to better predict micrometastases than IHC (39,40). To avoid false-positive results using IHC, the AJCC 5th edition indicates that node-negative disease can incorporate "isolated tumor cells" in the lymph nodes (i.e., histologically positive IHC and <0.2 mm) (25). These cells usually lack proliferative activity (http://www.cancerstaging.org). Futhermore, the AJCC 6th edition considers an IHC-positive and/or an RT-PCR–positive sample as N0i+ (isolated tumor cells by H & E or IHC, <0.2 mm) and N0(mol+) (no regional lymph node, but positive by RT–PCR) rather than N1 (1–3 positive lymph nodes or evidence of micrometastatic disease by SLNB) (17). Thus, while parallel use of IHC with H & E has increased the accuracy of staging slightly, its use is unlikely to have contributed to a stage-migratory effect (41) or to the increased incidence of stage IIA and stage IIB cancers, observed in this study.
Along with tumor size and type, patient age is an independent risk factor for axillary metastases in breast cancer (36). Like the study by Schouten et al. (7), we found increased breast cancer incidence during the 1990s in the United States, particularly among women aged 50–64 years (APC = 1.8%, 95% CI = 1.4 to 2.2) (data not shown). These peri- /postmenopausal women were also those invited to participate in population-based screening during the late 1980s and 1990s (38). Many of these women may also have used hormone replacement therapy (HRT) because 70%–80% of American gynecologists prescribed HRT for at least 10 years to women with an intact uterus after 1970 (42,43). HRT increases the risk of early-stage, low-grade, estrogen receptor–positive (ER+) breast cancers (37,43). Consistent with this, we observed substantially increased incidence of ER+ tumors. From 1990–2002, the incidence of stage IIB ER+ disease with micrometastatic lymph node involvement increased by 13.4% per annum (95% CI = 10.3 to 16.5) (Table 3). There were also increases of a slightly lower magnitude in the incidence of estrogen receptor–negative (ER–) tumors. For example, stage IIB ER– disease with micrometastatic lymph node involvement increased by 12.1% (95% CI = 5.5 to 19.1) (Table 3). It has been noted that women prescribed HRT often belong to higher social classes with better healthcare and screening access, thus increasing the likelihood of cancer detection at an earlier stage (44). Our findings, indicating consistent increases in micrometastatic disease for each stage and ER status, suggest that although HRT use may have contributed to the increased incidence of the ER+ breast tumors, HRT use cannot solely be responsible for this increased incidence because the incidence of ER– tumors with micrometastatic lymph node involvement also increased.
|
This population-based study tracked breast cancer incidence trends for a 12-year period (1990–2002), focusing primarily on early-stage disease. Limitations to our study include a) no adjustment for any sociodemographic factors (e.g., socioeconomic status, use of HRT, etc.) or for other clinical factors e.g., comorbidity, which may have impacted on a woman's tendency to attend screening and thereby facilitate diagnosis of their cancer at an earlier stage and b) before 1998, SEER did not identify the type of lymph node surgery—thus, it was not possible to estimate directly the extent of lymph node surgery in our patient population. We therefore could not determine the specific impact of SLNB on the incidence of breast tumors with micrometastatic lymph node involvement. Since then, however, the scope of lymph node surgery has been recorded for use in future studies.
Patients diagnosed with sentinel (pathologically confirmed) node-negative disease are believed to have a better prognosis than those with clinically confirmed node-negative disease (28,45,46). We have highlighted the increased incidence of early-stage breast cancer with lymph node involvement, specifically, cancer with micrometastatic lymph node involvement. While the use of SLNB in community practice continues to increase, it is expected that cases with lymph node metastases also will continue to increase.
|
Funding |
|---|
|
TopAbstractContext and CaveatsFundingReferencesNotes |
|---|
Funding to pay the Open Access publication charges for this article was provided by the Surveillance Research Program, National Cancer Institute.
|
NOTES |
|---|
|
TopAbstractContext and CaveatsFundingReferencesNotes |
|---|
Work carried out while at the Surveillance Research Program when Dr D. P. Cronin-Fenton was an All-Ireland/National Cancer Institute Cancer Consortium research fellow supported by the Health Research Board of Ireland.
The authors would like to acknowledge the contributions of the participating SEER registries and staffs. Without their dedicated efforts, this research could not have been conducted. The authors would like to thank the editors and reviewers for their constructive reviews. The authors would like to thank Ms Terri Harshman for her help in manuscript preparation.
|
REFERENCES |
|---|
|
TopAbstractContext and CaveatsFundingReferencesNotes |
|---|
(1) Chu KC, Tarone RE, Kessler LG, Ries LA, Hankey BF, Miller BA, et al. Recent trends in U.S. breast cancer incidence, survival, and mortality rates. J Natl Cancer Inst (1996) 88:1571–9.
(2) Harmer C, Staples M, Kavanagh AM. Evaluation of breast cancer incidence: is the increase due entirely to mammographic screening? Cancer Causes Control (1999) 10:333–7.[CrossRef][ISI][Medline]
(3) Miller BA, Feuer EJ, Hankey BF. Recent incidence trends for breast cancer in women and the relevance of early detection: an update. CA Cancer J Clin (1993) 43:27–41.[Abstract]
(4) Ghafoor A, Jemal A, Ward E, Cokkinides V, Smith R, Thun M. Trends in breast cancer by race and ethnicity. CA Cancer J Clin (2003) 53:342–55.
(5) Krag DN, Weaver DL, Alex JC, Fairbank JT. Surgical resection and radiolocalization of the sentinel lymph node in breast cancer using a gamma probe. Surg Oncol (1993) 2:335–9.[CrossRef][ISI][Medline]
(6) Giuliano AE, Dale PS, Turner RR, Morton DL, Evans SW, Krasne DL. Improved axillary staging of breast cancer with sentinel lymphadenectomy. Ann Surg (1995) 222:394–9.[ISI][Medline]
(7) Schouten LJ, de Rijke JM, Huveneers JA, Verbeek AL. Rising incidence of breast cancer after completion of the first prevalent round of the breast cancer screening programme. J Med Screen (2002) 9:120–4.
(8) Morton DL, Wen DR, Wong JH, Economou JS, Cagle LA, Storm FK, et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg (1992) 127:392–9.[Abstract]
(9) Nieweg OE, Estourgie SH. What is a sentinel node and what is a false-negative sentinel node? Ann Surg Oncol (2004) 11(Suppl:):169S–73S.
(10) Morton DL, Thompson JF, Essner R, Elashoff R, Stern SL, Nieweg OE, et al. Validation of the accuracy of intraoperative lymphatic mapping and sentinel lymphadenectomy for early-stage melanoma: a multicenter trial. Multicenter Selective Lymphadenectomy Trial Group. Ann Surg (1999) 230:453–63. discussion 463–5.
(11) Lyman GH, Giuliano AE, Somerfield MR, Benson AB 3rd, Bodurka DC, Burstein HJ, et al. American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. J Clin Oncol (2005) 23:7703–20.
(12) de Widt-Levert L, Tjan-Heijnen V, Bult P, Ruers T, Wobbes T. Stage migration in breast cancer: surgical decisions concerning isolated tumour cells and micro-metastases in the sentinel lymph node. Eur J Surg Oncol (2003) 29:216–20.[CrossRef][ISI][Medline]
(13) National Institutes of Health. NIH Consensus Conference. Treatment of early-stage breast cancer. JAMA (1991) 265:391–5.[CrossRef][ISI][Medline]
(14) Eifel P, Axelson JA, Costa J, Crowley J, Curran WJ Jr, Deshler A, et al. National Institutes of Health Consensus Development Conference statement: adjuvant therapy for breast cancer, November 1–3, 2000. J Natl Cancer Inst (2001) 93:979–89.
(15) Krag DN, Julian TB, Harlow SP, Weaver DL, Ashikaga T, Bryant J, et al. NSABP-32: phase III, randomized trial comparing axillary resection with sentinal lymph node dissection—a description of the trial. Ann Surg Oncol (2004) 11(Suppl):208S–10S.
(16) Hsueh EC, Giuliano AE. Sentinel lymph node technique for staging of breast cancer. Oncologist (1998) 3:165–70.
(17) Singletary SE, Connolly JL. Breast cancer staging: working with the sixth edition of the AJCC Cancer Staging Manual. CA Cancer J Clin (2006) 56:37–47.; quiz 50–1.
(18) National Comprehensive Cancer Network—Breast Cancer. (2007.) Available at: http://www.nccn.org. [Last accessed: June 13 , 2007.].
(19) Schwartz GF, Giuliano AE, Veronesi U. Consensus Conference Committee. Proceedings of the Consensus Conference on the Role of Sentinel Lymph Node Biopsy in Carcinoma of the Breast; 2001 Apr 19–22; Philadelphia (PA). Cancer (2002) 94:2542–51.[CrossRef][ISI][Medline]
(20) Giuliano A. Current status of sentinel lymphadenectomy in breast cancer. Ann Surg Oncol (2001) 8((Suppl)):52S–5S.[Medline]
(21) Maggard MA, Lane KE, O’Connell JB, Nanyakkara DD, Ko CY. Beyond the clinical trials: how often is sentinel lymph node dissection performed for breast cancer? Ann Surg Oncol (2005) 12:41–7.
(22) Rampaul RS, Miremadi A, Pinder SE, Lee A, Ellis IO. Pathological validation and significance of micrometastasis in sentinel nodes in primary breast cancer. Breast Cancer Res (2001) 3:113–6.[CrossRef][ISI][Medline]
(23) White RL Jr, Wilke LG. Update on the NSABP and ACOSOG breast cancer sentinel node trials. Am Surg (2004) 70:420–4.[ISI][Medline]
(24) Huvos AG, Hutter RV, Berg JW. Significance of axillary macrometastases and micrometastases in mammary cancer. Ann Surg (1971) 173:44–6.[ISI][Medline]
(25) Fleming ID, Cooper JS, Henson DE, Hutter RVP, Kennedy BJ, Murphy GP, et al. AJCC Cancer Staging Manual (1998) 5th ed. Philadelphia (PA): Lippincott Williams and Wilkins Publishers.
(26) Kim HJ, Fay MP, Feuer EJ, Midthune DN. Permutation tests for joinpoint regression with applications to cancer rates. Stat Med (2000) 19:335–51.[CrossRef][ISI][Medline]
(27) Clegg LX, Feuer EJ, Midthune DN, Fay MP, Hankey BF. Impact of reporting elay and reporting error on cancer incidence rates and trends. J Natl Cancer Inst (2002) 94:1537–45.
(28) Edge SB, Niland JC, Bookman MA, Theriault RL, Ottesen R, Lepisto E, et al. Emergence of sentinel node biopsy in breast cancer as standard-of-care in academic comprehensive cancer centers. J Natl Cancer Inst (2003) 95:1514–21.
(29) Noguchi M, Tsugawa K, Bando E, Kawahara F, Miwa K, Yokoyama K, et al. Sentinel lymphadenectomy in breast cancer: identification of sentinel lymph node and detection of metastases. Breast Cancer Res Treat (1999) 53:97–104.[CrossRef][ISI][Medline]
(30) Weaver D. Sentinel lymph nodes and breast carcinoma. Which micrometastases are clinically significant? Am J Surg Pathol (2003) 27:842–5.[CrossRef][ISI][Medline]
(31) Noguchi M. Current controversies concerning sentinel lymph node biopsy for breast cancer. Breast Cancer Res Treat (2004) 84:261–71.[CrossRef][ISI][Medline]
(32) Silberman AW, McVay C, Cohen JS, Altura JF, Brackert S, Sarna GP, et al. Comparative morbidity of axillary lymph node dissection and the sentinel lymph node technique: implications for patients with breast cancer. Ann Surg (2004) 240:1–6.[CrossRef][ISI][Medline]
(33) Pendas S, Jakub J, Giuliano R, Gardner M, Swor GB, Reintgen DS. The role of sentinel lymph node biopsy in patients with ductal carcinoma in situ or with locally advanced breast cancer receiving neoadjuvant chemotherapy. Cancer Control (2004) 11:231–5.[Medline]
(34) Dubernard G, Sideris L, Delaloge S, Marsiglia H, Rochard F, Travagli JP, et al. Quality of life after sentinel lymph node biopsy in early breast cancer. Eur J Surg Oncol (2004) 30:728–34.[CrossRef][Medline]
(35) Giuliano AE, Haigh PI, Brennan MB, Hansen NM, Kelley MC, Ye W, et al. Prospective observational study of sentinel lymphadenectomy without further axillary dissection in patients with sentinel node-negative breast cancer. J Clin Oncol (2000) 18:2553–9.
(36) Leidenius M, Krogerus L, Tukiainen E, von Smitten K. Accuracy of axillary staging using sentinel node biopsy or diagnostic axillary lymph node dissection–a case-control study. APMIS (2005) 112:264–70.[ISI]
(37) Li CI, Daling JR, Malone KE. Incidence of invasive breast cancer by hormone receptor status from 1992 to 1998. J Clin Oncol (2003) 21:28–34.
(38) Swan J, Breen N, Coates RJ, Rimer BK, Lee NC. Progress in cancer screening practices in the United States: results from the 2000 National Health Interview Survey. Cancer (2003) 97:1528–40.[CrossRef][ISI][Medline]
(39) Cody HS 3rd, Borgen PI, Tan LK. Redefining prognosis in node-negative breast cancer: can sentinel lymph node biopsy raise the threshold for systemic adjuvant therapy? Ann Surg Oncol (2004) 11(Suppl):227S–30S.
(40) Weaver DL, Krag DN, Manna EA, Ashikaga T, Waters BL, Harlow SP, et al. Detection of occult sentinel lymph node micrometastases by immunohistochemistry in breast cancer. An NSABP protocol B-32 quality assurance study. Cancer (2006) 107:661–7.[CrossRef][ISI][Medline]
(41) Aihara T, Munakata S, Morino H, Takatsuka Y. Comparison of frozen section and touch imprint cytology for evaluation of sentinel lymph node metastasis in breast cancer. Ann Surg Oncol (2004) 11:747–50.
(42) Brett KM, Madans JH. Use of postmenopausal hormone replacement therapy: estimates from a nationally representative cohort study. Am J Epidemiol (1997) 145:536–45.
(43) Pappo I, Meirshon I, Karni T, Siegelmann-Danielli N, Stahl-Kent V, Sandbank J, et al. The characteristics of malignant breast tumors in hormone replacement therapy users versus nonusers. Ann Surg Oncol (2003) 11:52–8.[CrossRef][ISI]
(44) Gapstur S, Morrow M, Sellers TA. Hormone replacement therapy and the risk of breast cancer with a favorable histology. JAMA (1999) 281:2091–7.
(45) Cserni G. Surgical pathological staging of breast cancer by sentinel lymph node biopsy with special emphasis on the histological work-up of axillary sentinel lymph nodes. Breast Cancer (2004) 11:242–9.[Medline]
(46) Imoto S, Wada N, Murakami K, Hasebe T, Ochiai A, Ebihara S. Prognosis of breast cancer patients treated with sentinel node biopsy in Japan. Jpn J Clin Oncol (2004) 34:452–6.
(47) de Widt-Levert L, Tjan-Heijnen V, Bult P, Ruers T, Wobbes T. Stage migration in breast cancer: surgical decisions concerning isolated tumour cells and micro-metastases in the sentinel lymph node. Eur J Surg Oncol (2003) 29:216–20.[CrossRef][ISI][Medline]
(48) Fleming ID, Cooper JS, Henson DE, Hutter RVP, Kennedy BJ, Murphy GP, et al. AJCC Cancer Staging Manual (1998) 5th Edition. Philadelphia (PA): Lippincott Williams and Wilkins Publishers.
(49) Miller BA, Feuer EJ, Hankey BF. Recent incidence trends for breast cancer in women and the relevance of early detection: an update. CA Cancer J Clin (1993) 43:27–41.[Abstract]
(50) Ghafoor A, Jemal A, Ward E, Cokkinides V, Smith R, Thun M. Trends in breast cancer by race and ethnicity. CA Cancer J Clin (2003) 53:342–55.
Manuscript received November 30, 2006; revised April 26, 2007; accepted May 23, 2007.
Related Articles in JNCI
CiteULike 
Connotea 
Del.icio.us What's this?
J Natl Cancer Inst 2007 99: 981.
J Natl Cancer Inst 2007 99: 981.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||