Breast Reconstruction: A Century of Controversies and Progress.

Breast cancer treatment has dramatically changed over the past century. Since Halsted's first description of radical mastectomy in 1882, breast reconstruction has evolved slowly from being considered as a useless or even dangerous procedure by surgeons to the possibility nowadays of reconstructing almost any kind of defect. In this review on the development of breast reconstruction, we outline the historical milestone innovations that led to the current management of the mastectomy defect in an attempt to understand the economic, social and psychological factors, which contributed to slow down its acceptance for several decades.

Impact of family history of breast cancer on tumour characteristics, treatment, risk of second cancer and survival among men with breast cancer.

BACKGROUND: Male breast cancer patients have a higher risk of developing a second primary cancer, but whether this risk differs according to the family history of breast or ovarian cancers remains to be elucidated. We aimed to determine the effect of a positive family history among men diagnosed with breast cancer on tumour characteristics, treatment, second cancer occurrence and overall survival. METHODS: We included 46 patients with known information on the family history of breast or ovarian cancer recorded at the Geneva Cancer Registry between 1970 and 2009. We compared patients with and without a family history with chi-square of heterogeneity, risk of second cancer with standardised incidence ratios (SIRs), and overall survival by Kaplan-Meier methods. RESULTS: Approximately 20% of men with breast cancer had a positive family history. No differences were observed between men with and without familial risk except that patients with increased risk were more likely to receive radiotherapy and hormone therapy when compared with patients without familial risk. This more complete therapy is likely to be explained by the heightened awareness of cancer treatment among breast cancer patients with affected family members. Six men developed a second cancer. SIRs for second cancer were not significantly increased among patients with or without familial risk (1.93, 95% confidence interval [CI] 0.23-6.97 and 1.04, 95% CI 0.28-2.66, respectively). Overall survival was not significantly different between the two groups. CONCLUSIONS: Prognosis was similar among patients with or without familial risk. Our results are however based on small numbers and larger registry-based cohorts of males with precise data on familial risk are still warranted.

Other primary malignancies in breast cancer patients treated with breast conserving surgery and radiation therapy.

BACKGROUND: Our purpose was to examine the incidence and impact on survival of other primary malignancies (OPM) outside of the breast in breast cancer patients and to identify risk factors associated with OPM. METHODS: Patients with stage 0-III breast cancer treated with breast conserving therapy at our center from 1979 to 2007 were included. Risk factors were compared between patients with/without OPM. Logistic regression was used to identify factors that were associated with OPM. Standardized incidence ratios (SIRs) were calculated. RESULTS: Among 4,198 patients in this study, 276 (6.6 %) developed an OPM after breast cancer treatment. Patients with OPM were older and had a higher proportion of stage 0/I disease and contralateral breast cancer compared with those without OPM. In a multivariate analysis, older patients, those with contralateral breast cancer, and those who did not receive chemotherapy or hormone therapy were more likely to develop OPM after breast cancer. Patients without OPM had better overall survival. The SIR for all OPM sites combined after a first primary breast cancer was 2.91 (95 % confidence interval: 2.57-3.24). Significantly elevated risks were seen for numerous cancer sites, with SIRs ranging from 1.84 for lung cancer to 5.69 for ovarian cancer. CONCLUSIONS: Our study shows that breast cancer patients have an increased risk of developing OPM over the general population. The use of systemic therapy was not associated with increased risk of OPM. In addition to screening for a contralateral breast cancer and recurrences, breast cancer survivors should undergo screening for other malignancies.

Diagnostic and prognostic correlates of preoperative FDG PET for breast cancer.

PURPOSE: To explore the preoperative utility of FDG PET for the diagnosis and prognosis in a retrospective breast cancer case series. METHODS: In this retrospective study, 104 patients who had undergone a preoperative FDG PET scan for primary breast cancer at the UZ Brussel during the period 2002-2008 were identified. Selection criteria were: histological confirmation, FDG PET performed prior to therapy, and breast surgery integrated into the primary therapy plan. Patterns of increased metabolism were recorded according to the involved locations: breast, ipsilateral axillary region, internal mammary chain, or distant organs. The end-point for the survival analysis using Cox proportional hazards was disease-free survival. The contribution of prognostic factors was evaluated using the Akaike information criterion and the Nagelkerke index. RESULTS: PET positivity was associated with age, gender, tumour location, tumour size >2 cm, lymphovascular invasion, oestrogen and progesterone receptor status. Among 63 patients with a negative axillary PET status, 56 (88.9 %) had three or fewer involved nodes, whereas among 41 patients with a positive axillary PET status, 25 (61.0 %) had more than three positive nodes (P < 0.0001). In the survival analysis of preoperative characteristics, PET axillary node positivity was the foremost statistically significant factor associated with decreased disease-free survival (hazard ratio 2.81, 95% CI 1.17-6.74). CONCLUSION: Preoperative PET axillary node positivity identified patients with a higher burden of nodal involvement, which might be important for treatment decisions in breast cancer patients.

Risk, characteristics, and prognosis of breast cancer after Hodgkin's lymphoma.

PURPOSE: To assess breast cancer (BC) risk after Hodgkin's lymphoma (HL) and compare characteristics, risk of second BC, and prognosis of patients with these BCs with patients with first primary BC. PATIENTS AND METHODS: We considered all 9,620 women with HL recorded in the Surveillance, Epidemiology and End Results dataset in 1973-2007. We calculated age-period standardized incidence ratios of BC. We compared patient, tumor, and treatment characteristics, risk of second BC, and prognosis between patients with BC after HL (n = 316) and patients with other BCs occurring during the same period (n = 450,413) using logistic regression and Cox models adjusted for confounders. RESULTS: HL patients had a 2.4-fold higher risk for developing BC (95% confidence interval [CI], 2.2-2.7) than the general population. Age at HL diagnosis and radiation therapy influenced this risk. Compared with first primary BCs, BCs after HL were diagnosed at a younger age, at an earlier stage, were less frequently hormone receptor positive, were located more frequently in external quadrants, and were less frequently treated using radiotherapy. These patients had a higher risk (adjusted hazard ratio [HR], 2.85; 95% CI, 1.79-4.53) for developing a second BC and had a higher BC mortality risk (adjusted HR, 1.36; 95% CI, 1.05-1.76). The higher mortality risk was only partly explained by the higher occurrence rate of a second BC. CONCLUSION: HL survivors have a higher risk for developing BC, their BCs are more aggressive, they have a higher risk for a second BC occurrence, and they have a poorer prognosis. Guidelines of care should be adapted to decrease the impact of BC in these high-risk patients.

Antiestrogen therapy for breast cancer modifies the risk of subsequent cutaneous melanoma.

Increased risk of secondary melanoma after breast cancer has been reported. Several lines of evidence suggest that elevated estrogen levels may be implicated in melanoma etiology. Accordingly, use of antiestrogens should be associated with decreased risk of melanoma. We compared melanoma incidence among a cohort of breast cancer patients with and without antiestrogen therapy, with data from the Geneva Cancer Registry. The cohort consisted of 7,360 women diagnosed with breast cancer between 1980 and 2005. About 54% of these patients received antiestrogens. All women were followed until December 2008. We compared cutaneous melanoma incidence rates among patients with and without antiestrogens with those expected in the general population by age and period standardized incidence ratios (SIR). A total of 34 women developed a melanoma during the follow-up period. Compared with the general population, the risk of melanoma was higher for patients who did not receive antiestrogens (SIR: 1.60, 95% CI: 1.08-2.12, P = 0.02). On the contrary, the risk was close to 1 (SIR: 0.98, 95% CI: 0.40-1.56, P = 0.57) for patients who received antiestrogen therapy. This study suggests that antiestrogen therapy modifies the risk of melanoma after breast cancer. Although our results are in agreement with the hypothesis that estrogens could play a role in melanoma occurrence, they need to be replicated in a larger study with data on potential confounders. .

Breast cancer prognosis is inherited independently of patient, tumor and treatment characteristics.

Population-based studies have shown a concordance of breast cancer survival among first-degree relatives (FDRs), suggesting a heritable component. Reasons for such heritability remain to be elucidated. We aimed to determine whether association of breast cancer survival among FDRs is linked to shared patient and tumor characteristics or type of treatment. At the population-based Geneva Breast Cancer Registry, we identified 162 FDR pairs diagnosed with breast cancer. We categorized FDRs into poor, medium and good familial survival risk groups according to breast cancer-specific survival of their proband (mother or sister). We compared patient, tumor and treatment characteristics between categories and calculated standardized mortality ratios (SMRs) and adjusted disease-specific mortality for each group. Breast cancer patients in the poor familial survival risk group were more likely to be diagnosed at later stages than those in the good familial survival risk group. Similarly, they had higher SMRs than those in the medium and good survival risk groups (18.7, 95% confidence interval [CI]: 9.4-33.5 vs. 16.5, 95% CI: 7.5-31.3 and 9.4, 95% CI: 3.4-20.4, respectively). After adjustment for patient and tumor characteristics and type of treatment, women in the poor familial survival risk group were almost five times more likely to die of breast cancer than those in the good familial survival risk group (adjusted hazard ratio 4.8, 95% CI: 1.4-16.4). Our study shows that breast cancer prognosis clusters within families and suggests that the hereditary component is independent of patient and tumor characteristics and type of treatment.

Lung cancer mortality risk among breast cancer patients treated with anti-estrogens.

BACKGROUND: The Women's Health Initiative randomized clinical trial reported that menopausal hormone therapy increases lung cancer mortality risk. If this is true, use of anti-estrogens should be associated with decreased lung cancer mortality risk. The authors compared lung cancer incidence and mortality among breast cancer patients with and without anti-estrogen therapy. METHODS: Our study included all 6655 women diagnosed with breast cancer between 1980 and 2003 and registered at the Geneva Cancer Registry. Among these women, 46% (3066) received anti-estrogens. All women were followed for occurrence and death from lung cancer until December 2007. The authors compared incidence and mortality rates among patients with and without anti-estrogens with those expected in the general population by Standardized Incidence Ratios (SIRs) and Standardized Mortality Ratios (SMRs). RESULTS: After a total of 57,257 person-years, 40 women developed lung cancer. SIRs for lung cancer were not significantly decreased among breast cancer patients with and without anti-estrogens (0.63, 95% confidence intervals [CI], 0.33-1.10; and 1.12, 95% CI, 0.74-1.62, respectively) while SMR was decreased among women with anti-estrogens (0.13, 95% CI, 0.02-0.47, P<.001) but not for women without anti-estrogens (0.76, 95% CI, 0.43-1.23). CONCLUSIONS: Compared with expected outcomes in the general population, breast cancer patients receiving anti-estrogen treatment for breast cancer had lower lung cancer mortality. This study further supports the hypothesis that estrogen therapy modifies lung cancer prognosis.

Risk of second breast cancer according to estrogen receptor status and family history.

A recent study reported an increased risk of contralateral estrogen-negative breast cancer after a first primary estrogen-negative breast cancer. Our study aims to confirm this result and to evaluate how the risk of second breast cancer occurrence is affected by family history of breast cancer and anti-estrogen treatment. We included all 4,152 women diagnosed with breast cancer between 1995 and 2007, using data from the population-based Geneva Cancer Registry. We compared the incidence of second breast cancer among patients according to estrogen receptor (ER) status with that expected in the general population by age-period Standardized Incidence Ratios (SIRs). Among the cohort, 63 women developed second breast cancer. Patients with ER-positive first tumors had a decreased risk of second breast cancer occurrence (SIR: 0.67, 95% CI: 0.48-0.90), whereas patients with ER-negative primary tumors had an increased risk (SIR: 1.98, 95% CI: 1.19-3.09) limited to ER-negative second tumors (SIR: 7.94, 95% CI: 3.81-14.60). Patients with positive family history had a tenfold (SIR: 9.74, 95% CI: 3.57-21.12) higher risk of ER-negative second tumor which increased to nearly 50-fold (SIR: 46.18, 95% CI: 12.58-118.22) when the first tumor was ER-negative. Treatment with anti-estrogen decreased the risk of second ER-positive tumors but not ER-negative tumors. The risk of second ER-negative breast cancer is very high after a first ER-negative tumor, in particular among women with strong family history. Surveillance and prevention of second cancer occurrence should consider both ER status of the first tumor and family history.

Age and axillary lymph node ratio in postmenopausal women with T1-T2 node positive breast cancer.

PURPOSE: The purpose of this article was to examine the relationship between age and lymph node ratio (LNR, number of positive nodes divided by number of examined nodes), and to determine their effects on breast cancer (BC) and overall mortality. METHODS: Women aged ≥50 years, diagnosed in 1988-1997 with a unilateral histologically confirmed T1-T2 node positive surgically treated primary nonmetastatic BC, were selected from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER). Generalized Additive Models for Location Scale and Shape (GAMLSS) were used to evaluate the age-LNR relationship. Cumulative incidence functions and multivariate competing risks analysis based on model selection by the Bayesian Information Criterion (BIC) were used to examine the effect of age and LNR on mortality. Low LNR was defined as ≤0.20, mid-LNR 0.21-0.65, and high LNR >0.65. RESULTS: GAMLSS showed a nonlinear LNR-age relationship, increasing from mean LNR 0.26-0.28 at age 50-70 years to 0.30 at 80 years and 0.40 at 90 years. Compared with a 9.8% [95% confidence interval (CI) 8.8%-10.8%] risk of BC death at 5 years in women aged 50-59 years with low LNR, the risk in women ≥80 years with low LNR was 12.6% [95% CI 10.1%-15.0%], mid-LNR 18.1% [13.9%-22.1%], high LNR 29.8% [22.7%-36.1%]. Five-years overall risk of death increased from 40.8% [37.5%-43.9%] by low LNR to 67.4% [61.4%-72.4%] by high LNR. The overall mortality hazard ratio for age ≥80 years with high LNR was 7.49 [6.54-8.59], as compared with women aged 50-59 years with low LNR. CONCLUSION: High LNR combined with older age was associated with a threefold increased risk of BC death and a sevenfold increased hazard ratio of overall mortality.

Comparison of women's breast cancer risk factors in Geneva, Switzerland and Shanghai, China.

BACKGROUND: We compared the prevalence of known and suspected breast cancer risk factors among women in Geneva, Switzerland, where the annual incidence of breast cancer is high, to women in Shanghai, China, where incidence is lower. METHODS: Different translations of the same woman's health questionnaire were administered to women aged 35 to 74 years in Shanghai (n=631) and Geneva (n=1,212) during 1996-1997 and reproductive and lifestyle factors compared. RESULTS: Shanghai women reported older age at menarche (median 15 vs. 13 years), fewer nulliparity (7.3 vs. 21.6%), younger age at first live birth (median 25.7 vs. 28.4 years), and shorter duration of reproductive life (median 35.7 vs. 38.4 years). Geneva women had a greater prevalence of current cigarette smoking (22.4 vs. 1.8%), oral contraceptive use (61.1 vs. 10.0%), hormone replacement therapy use (23.4 vs. 0.8%), and family history of breast cancer (8.6 vs. 1.4%). Among women who breastfed, Shanghai women had more than twice the duration of breastfeeding than Geneva women (median 48 vs. 21 weeks). CONCLUSIONS: Differences in the prevalence of breast cancer risk factors, in particular reproductive characteristics, may contribute to the large contrast in cumulative risk between women living in Geneva and Shanghai.

Local-regional radiotherapy and surgery is associated with a significant survival advantage in metastatic breast cancer patients.

BACKGROUND: There is growing evidence of a survival benefit for metastatic breast cancer patients receiving surgery of the primary tumor. We investigated whether or not adjuvant radiotherapy can improve survival. METHODS: Women diagnosed between 1988 and 2003 with metastatic, histologically confirmed unilateral primary breast cancer were selected from the SEER Program. Overall survival and specific survival were computed by the Kaplan-Meier method. Treatment hazard ratios of breast-conserving surgery or mastectomy versus no surgery, and radiotherapy versus none, were computed by Cox regression adjusting for period of diagnosis, age, marital status, race, histology, grade, and hormone receptors. RESULTS: Of 8761 women, radiotherapy was given to 1473 of 3905 who did not undergo surgery, to 882 of 2070 who underwent breast-conserving surgery, and to 1103 of 2786 mastectomy patients. Median overall survival was: for no surgery, 14 months; for breast-conserving surgery, 23 months; and for mastectomy, 28 months (P < 0.0001). The median overall survival of radiotherapy versus none was respectively 16 vs. 13 months without surgery (P = 0.0003), 28 vs. 20 months for breast-conserving surgery patients (P < 0.0001), and 28 vs. 28 months among mastectomy patients (P = 0.895). Multivariate analysis showed relative mortality reductions of 28% by breast-conserving surgery, 42% by mastectomy, and 10% by radiotherapy. Specific survival showed comparable results. CONCLUSIONS: Surgery and radiotherapy were associated with a significant survival advantage. We argue that local therapy should be considered even in metastatic disease.

Loco-regional treatment in metastatic breast cancer patients: is there a survival benefit?

A number of studies have recently demonstrated a survival benefit in stage IV breast cancer patients following surgical resection of the primary tumor. Here, we investigate the relationship between loco-regional treatment and survival in patients with metastatic breast cancer and evaluate the impact of different loco-regional treatments. We conducted a systematic review of the literature using PubMed to analyze studies with the following criteria: Type of loco-regional treatment (surgery alone or combined with radiation, radiotherapy), overall survival, progression-free survival, selection factors for local treatment, and complication rates. Thirteen studies evaluated the effect of loco-regional treatment on overall survival with overall median survival increasing from a range of 12.6-28.3 months among patients without surgery to a range of 25-42 months among patients with surgery. In addition, six studies reported a 3-year survival benefit of 28-95% and 17-79% in women with and without locoregional therapy respectively. Two studies did not find any improvement in overall survival. One study found an improvement in 5-year breast cancer-specific survival of 27% with negative surgical margins versus 12% with no surgery. Three studies reported an advantage in progression-free survival in the treatment group compared with the non-treatment group. Loco-regional treatment for breast cancer patients with distant metastases at diagnosis is an important issue because of possible improvement of survival or disease-free survival. The possibility of surgery and/or radiotherapy following induction chemotherapy should be weighed and left to individual practice. Participation in randomized controlled trials should be encouraged.

Changing pattern of age-specific breast cancer incidence in the Swiss canton of Geneva.

Hormone replacement therapy (HRT) use declined sharply after mid-2002, when the Women's Health Initiative trial reported an association between breast cancer occurrence and HRT. Hypothesized mechanism behind this association is that HRT promotes growth of pre-existing small tumors, leading to earlier tumor detection. We evaluated the impact of the sudden decline in HRT use on age distribution of breast cancer in Geneva. We included all incident breast cancer cases recorded from 1975 to 2006 at the Geneva cancer registry. We calculated mean annual incidence rates per 100,000 for 2 year periods for three age groups and assessed temporal changes by joinpoint regression. We compared age-specific incidence curves for different periods, reflecting different prevalence rates of HRT use. After increasing constantly between 1986 and 2002 among women aged 50-69 years [annual percent change (APC): +4.4, P < 0.0001], rates declined sharply after 2003 (APC: -6.0; P = 0.0264). Age-specific breast cancer rates changed dramatically with changes in prevalence of HRT use. During low HRT prevalence, breast cancer incidence increased progressively with age, when HRT prevalence was reaching its maximum (1995-2002), higher rates were seen in 60- to 64-year-old women, with a concomitant decrease in risk among elderly. After the sudden decline in HRT use, the incidence peak diminished significantly and incidence increased again with age. Following the abrupt decline in HRT use in Geneva, breast cancer incidence rates among post-menopausal women decreased considerably with striking changes in age-specific incidence rates before, during and after the peak in HRT prevalence.

Endometriosis related to family history of malignancies in the Yale series.

OBJECTIVE: Recent studies reported that endometriosis could behave as a neoplasmatic process. The purpose of this study is to investigate the family risk of ovarian, colon and prostate cancer in women with endometriosis. STUDY DESIGN: A search of medical records at the Yale New Haven Hospital from 1996 to 2002 identified 348 women with endometriosis and 179 women without endometriosis. All the cases were diagnosed by laparoscopy. Demographic characteristics were evaluated in women with positive or negative family history of cancers in women with endometriosis. RESULTS: The overall risk of patients with endometriosis and positive family history of cancers was 7.7 (95% confidence interval 3.8-15.7) (chi(2)=39.8, P<0.001). Significant excess was observed for ovarian cancer in first- and second-degree relatives (OR=10.5, 95% CI (2.5-44.2), chi(2)=14.3, P<0.001), colon cancer (OR=7.5, 95% CI (2.7-21.1), chi(2)=18.2, P<0.001) and prostate cancer (OR=4.5, 95% CI (14-15.3), chi(2)=6.1, P<0.001). We found similar results in first- and second-degree relatives with ovarian and colon cancer. Moreover, we found similar results regarding the demographic characteristics in women with positive family history of cancers and in women with negative history. CONCLUSIONS: These data suggest a familial association of endometriosis with ovarian, colon and prostate cancers. This evidence could support the genetics and molecular similarities between endometriosis and cancer. Future studies will be important to determine a clear genetic link between endometriosis and cancer.

Impact of obesity on diagnosis and treatment of breast cancer.

In this population-based study, we evaluated the impact of obesity on presentation, diagnosis and treatment of breast cancer. Among all women diagnosed with invasive breast cancer in the canton Geneva (Switzerland) between 2003 and 2005, we identified those with information on body mass index (BMI) and categorized them into normal/underweight (BMI <25 kg/m(2)), overweight (BMI > or =-<30 kg/m(2)) and obese (BMI > or =30 kg/m(2)) women. Using multivariate logistic regression, we compared tumour, diagnosis and treatment characteristics between groups. Obese women presented significantly more often with stage III-IV disease (adjusted odds ratio [OR(adj)]: 1.8, 95% CI: 1.0-3.3). Tumours > or =1 cm and pN2-N3 lymph nodes were significantly more often impalpable in obese than in normal/underweight patients (OR(adj) 2.4, [1.1-5.3] and OR(adj) 5.1, [1.0-25.4], respectively). Obese women were less likely to have undergone ultrasound (OR(adj) 0.5, [0.3-0.9]) and MRI (OR(adj) 0.3, [0.1-0.6]) and were at increased risk of prolonged hospital stay (OR(adj) 4.7, [2.0-10.9]). This study finds important diagnostic and therapeutic differences between obese and lean women, which may impair survival of obese women with breast cancer. Specific strategies are needed to optimize the care of obese women with or at risk of breast cancer.

Prognostic value of nodal ratios in node-positive breast cancer: a compiled update.

The number of positive axillary nodes is a strong prognostic factor in breast cancer, but is affected by variability in nodal staging technique yielding varying numbers of excised nodes. The nodal ratio of positive to excised nodes is an alternative that could address this variability. Our 2006 review found that the nodal ratio consistently outperformed the number of positive nodes, providing strong arguments for the use of nodal ratios in breast cancer staging and management. New evidence has continued to accrue confirming the prognostic significance of nodal ratios in various worldwide population settings. This review provides an updated summary of available data, and discusses the potential application of the nodal ratio to breast cancer staging and prognostication, its role in the context of modern surgical techniques such as sentinel node biopsy, and its potential correlations with new biologic markers such as circulating tumor cells and breast cancer stem cells.

The effect of adjuvant radiotherapy on mortality differs according to primary tumor location in women with node-positive breast cancer.

PURPOSE: To evaluate the prognostic significance of primary tumor location and to examine whether the effect of adjuvant radiotherapy on survival varies according to tumor location in women with axillary node-positive (ALN+) breast cancer (BC). PATIENTS AND METHODS: Data were abstracted from the SEER database for 24,410 women aged 25-95 years, diagnosed between 1988-1997 with nonmetastatic T1-T2, ALN+ BC. Subgroup analyses were performed using interactions within proportional hazards models. Event was defined as death from any cause. Prognostic variables were selected using Akaike Information Criteria. Joint significances of subgroups were evaluated with Wald test. RESULTS: Median follow-up was 10 years. In joint models, statistically significant interactions were found between tumor location, nodal involvement, type of surgery, and radiotherapy. Factorial presentation of interactions showed consistent 13% proportional reduction of mortality in all subgroups, except in women with medial tumors with > or = 4 ALN+ treated with mastectomy. In this subgroup, use of radiotherapy was associated with a 16% proportional increase in mortality. CONCLUSION: Medial tumor location is a significant adverse prognostic factor that should be considered in treatment decision- making for women with ALN+ BC. Improved survival was observed with radiotherapy use in all subgroups, except in women with medial tumors with > or = 4 ALN+ treated with postmastectomy radiotherapy. These findings raise concern that the favorable effect of radiotherapy may be offset by excess toxicities in the latter subgroup.

Lymph node ratio as an alternative to pN staging in node-positive breast cancer.

PURPOSE: In the current pTNM classification system, nodal status of breast cancer is based on the number of involved lymph nodes and does not account for the total number of lymph nodes removed. In this study, we assessed the prognostic value of the lymph node ratio (LNR; ie, ratio of positive over excised lymph nodes) as compared with pN staging and determined its optimal cutoff points. PATIENTS AND METHODS: From the Geneva Cancer Registry, we identified all women diagnosed with node-positive breast cancer between 1980 and 2004 (n = 1,829). The prognostic value of LNRs was calculated for values ranging from 0.05 to 0.95 by Cox regression analysis and validated by bootstrapping. Based on maximum likelihood, we identified cutoff points classifying women into low-, intermediate-, and high-risk LNR groups. RESULTS: Optimal cutoff points classified patients into low- (< or = 0.20), intermediate- (> 0.20 and < or = 0.65), and high-risk (> 0.65) LNR groups, corresponding to 10-year disease-specific survival rates of 75%, 63%, and 40%, and adjusted mortality risks of 1 (reference), 1.78 (95% CI, 1.46 to 2.18), and 3.21 (95% CI, 2.54 to 4.06), respectively. In contrast to LNR risk categories, survival curves of pN2 and pN3 crossed after 15 years, and their adjusted mortality risks showed overlapping CIs: 2.07 (95% CI, 1.69 to 2.53) and 2.84 (95% CI, 2.23 to 3.61), respectively. CONCLUSION: LNR predicts survival after breast cancer more accurately than pN classification and should be considered as an alternative to pN staging.