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30th Charles A. Coltman San Antonio Breast Cancer Symposium (SABCS)
December 13-16, 2007, SanAntonio, Texas, USA
Ion Chiricuta Cancer Center Cluj-Napoca, Dept. of Breast Tumors The 30th Charles A. Coltman San Antonio Breast Cancer Symposium (SABCS) took place on December 13-16, 2007, in San Antonio, Texas. Important clinical and research data presented during this prestigious meeting dedicated to breast cancer is reviewed in this ma-terial. Key words: Breast Cancer, Clinical Research.
830010participants from over 80 countries met in December in San Antonio, Texas to present the latest positive tumors, receipt of 5 years of tamoxifen con-research, treatment methods, and exchange knowledge ferred an absolute 9% reduction in 15-year breast can-about breast cancer. SABCS is one of the best breast cer mortality without any significant effect on non-cancer research meetings in the world, which is why the breast-cancer mortality. The curves further diverged American Association for Cancer Research (AACR) during the decade after stopping tamoxifen, underlining announced that they will collaborate on future Breast the carry-over effect of tamoxifen. Women with ER-Cancer Symposiums, to create the most comprehensive positive disease had slightly lower 5-year breast cancer meetings on breast cancer. 2007 marks the 30th year mortality if they received 5 years of an aromatase in-that the San Antonio Breast Cancer Symposium has hibitor, compared with 5 years of tamoxifen (6.5% vs convened, and the growth from the initial 100 partici- 7.4%), although this was not statistically significant. Finally, taking into account data on the relative The opening plenary lecture was given by Sir
benefits of CMF, anthracycline-based regimens, and Richard Peto, who presented results of the 2005-2006
taxane-containing regimens, the risk of breast cancer update of the worldwide overview of breast cancer ad- mortality was reduced with anthracycines and taxane juvant treatment, on behalf of the Early Breast Cancer chemotherapy by one-half among women younger than Trialists' Collaborative Group. The overview is based age 50 (rate ratio, 0.46) and by one-third among women on data from roughly 350,000 women and 400 random- Dr. Peto concluded that middle-aged women In the meta-analysis, radiation therapy after today are about half as likely as their counterparts 25 mastectomy with axillary nodal dissection conferred an years ago to die from breast cancer, thanks in large part absolute reduction of breast cancer mortality at 15 years to the collective effects of modern therapies. of 7% to 8%. All-cause mortality was reduced 5% to Donald A. Berry and colleagues at the M.D.
6% among women with positive nodes, according to Anderson Cancer Center and European Group for Dr. Peto. In contrast, among women with node-negative Blood and Marrow Transplantation presented a disease, this treatment increased all-cause mortality. metaanalysis of high-dose chemotherapy (HDC) with autologus stem cell support in breast cancer. They ana-lyzed individual patient data from 15 randomized trials among 6210 women with node-positive breast cancer, Journal of Radiotherapy & Medical Oncology assigned to either HDC with autologous stem cell transplantation or SDC. With a 7-year median follow- Address for correspondence: Alexandru Eniu up, relapse-free survival was significantly better in the HDC group than in the SDC group in the entire popula- tion (hazard ratio, 0.87), but overall survival was not A. Eniu: 30th Charles A. Coltman San Antonio Breast Cancer Symposium (hazard ratio, 0.94). HDC had no significant overall on amplification or overexpression of the topoisom-survival benefit relative to SDC when women were erase IIα (topo IIα) gene. The topo IIα gene encodes an stratified by age (<50 vs ≥50 years), menopausal status, enzyme that is critical in DNA replication and function, number of positive nodes (<10 vs ≥10), tumor size (<2 and the topo IIα protein is a major target of the anthra-vs ≥2 cm), hormone receptor status (positive vs nega- cyclines. Given that topo IIα amplification occurs only tive), histology (infiltrating ductal carcinoma vs infil- in about one-third of the HER2+ patient population, or trating lobular carcinoma), and HER-2/neu status (posi- "a subset of a subclass," Dr. Slamon questioned the tive vs negative). Survival after relapse did differ de- preferential use of anthracyclines in the HER2– popula- pending on the treatment -- but not in favor of HDC: "If tion, which represents about 75% of all breast cancers. you had standard therapy and relapse, you do better A recent analysis of the BCIRG 006 (HER2+ patients) than if you had high-dose therapy," Dr. Berry said. He and BCIRG 005 (HER2-normal patients) trials revealed concluded that when used as adjuvant therapy for node- that topo IIα amplification is observed in about 35% of positive breast cancer, the combination of high-dose HER2+ patients and is confined to cancers that contain chemotherapy (HDC) and stem cell transplantation the HER2 amplicon. BCIRG 006 randomized 3222 pa-modestly improves relapse-free survival relative to tients to doxorubicin/cyclophosphamide followed by standard-dose chemotherapy (SDC), with little or no docetaxel (AC-T), to AC-T plus trastuzumab (AC-TH), benefit on overall survival. or to an experimental non-anthracycline-based regimen Stephen Jones presented an updated analysis,
of docetaxel, carboplatin, and trastuzumab (TCH). The with a median of 7 years follow-up, of a randomized efficacy observed with AC-TH was restricted to pa-trial of four cycles of TC compared with four cycles of tients with coamplification of HER2 and topo IIα. In AC in 1016 women with node-negative and node- noncoamplified patients, 4-year disease-free survival positive early breast cancer. They previously showed a was 83% for AC-TH, 81% for TCH, and 71% for AC-disease-free survival benefit for the non-anthracycline T. But in coamplified patients, disease-free survival was arm at 5 years. Patients with stage I, II, or operable similar for all groups (83% to 85%). Their conclusion is stage III invasive breast cancer were randomized to four that the incremental efficacy benefit attributed to an-cycles every 21 days of doxorubicin 60 mg/m2 plus thracycline-based therapies is restricted to the HER2+ cyclophosphamide 600 mg/m2 or to docetaxel 75 subgroup. These data await peer-review and publication mg/m2 plus cyclophosphamide 600 mg/m2. The study before they can be used in clinical practice. excluded patients who had received neoadjuvant che- Tim Whelan presented long-term results, at 12
motherapy and those with tumors >7 cm or <1 cm. The years of follow-up, of their study comparing accelerated current analysis was based on a median follow-up of 7 hypofractionated whole-breast irradiation (AHWBI) years. versus standard whole-breast irradiation (SWBI). Disease-free survival was 81% for the TC arm Whole breast irradiation (WBI) is an integral part of and 76% for the AC arm, for a relative risk reduction of breast-conserving therapy in that it reduces the risk of 26% favoring TC (P = .03). Overall survival was 87% local recurrence and avoids mastectomy. Yet despite its for TC and 82% for AC, for a 31% relative risk reduc- benefits, up to 30% of women do not receive this treat- tion at 7 years (P = .03). In the older patients, TC was ment, largely because of inconvenience and cost. associated with slightly more febrile neutropenia but WBI is usually given as 50 Gy (2 Gy daily) in with less anemia than AC and with less long-term tox- 25 fractions over 5 weeks, with or without boost irra- diation. Data from trials in the U.K. and Canada have With longer follow-up, compared with standard suggested that accelerated and/or hypofractionated (lar- treatment with doxorubicin /cyclophosphamide (AC), ger dose per fraction) WBI can be just as effective. This four cycles of docetaxel (Taxotere) plus cyclophos- approach involves less treatment time for the patient, phamide (TC) improved both disease-free and overall giving 40 to 42.5 Gy in 15 or 16 fractions over 3 weeks survival in the extended follow-up and analysis of US in daily fractions of 2.7 Gy. Oncology Adjuvant Trial 9735. The study presented by Dr. Whelan recruited Dennis Slamon and colleagues performed a 1234 node-negative patients who had undergone lum-
systemic review of published data from randomized pectomy between 1993 and 1996 and randomized them controlled adjuvant trials that classified patients by to SWBI or AHWBI. The SWBI approach treated the HER2 subtype, and they reclassified the BCIRG 005 whole breast in two opposed tangential fields and used and 006 trials according to topo IIα coamplification. wedge compensation to assure a uniform dose at mid-The superior efficacy benefits for anthracyclines, when field. Updated results from the study presented at present, appear to derive from the effect of these agents SABCS showed local recurrence rates to be 6.2% for Journal of Radiotherapy & Medical Oncology, March 2008 Vol. XIV No. 1:54-59 SWBI and 6.7% for AHWBI. Overall survival was venting bone loss in postmenopausal women on AI 84.4% and 84.6%, respectively. Local recurrence rates therapy at 36 months of follow-up, as shown by in-were higher for patients <50 years of age, patients with creased lumbar spine and total hip BMD. Bone-specific larger tumor size, and patients not receiving systemic alkaline phosphatase and serum NTX were effectively therapy, but there were no differences according to suppressed. No differences were seen in symptomatic treatment arm. or asymptomatic fracture rates at 36 months with up- Cosmetic outcome, an indication of late mor- front therapy. There was a trend towards lower disease bidity, was assessed by trained clinical trials nurses ac- recurrence with upfront therapy. Zoledronic acid was cording to the EORTC Cosmetic Rating System. The safe and well tolerated. percentage of patients deemed to have excellent or good Sir Richard Peto presented the early results of
cosmetic outcome at 10 years was 71% with SWBI and the international trial ATLAS that randomized 11,500 70% with AHWBI. Late radiation morbidity was also women with treated breast cancer who had completed 5 similar, observed in skin in 8% and 9%, respectively, years of tamoxifen therapy to either continue taking the and in subcutaneous tissue in 11% and 12%, respec- drug for 5 more years or stop taking it. tively. No patients developed grade 4 toxicity. The au- Estrogen receptor (ER) status was positive in thors concluded that after breast-conserving surgery, a 59% of the patients and untested in 41% (therefore, shorter radiotherapy regimen is as effective and cos- 90% were estimated to be ER-positive). Halfway metically acceptable as a standard technique. through the trial, 83% in the longer-duration group There were a number of presentations related to were taking tamoxifen as were 4% in the shorter- bone loss in patients receiving aromatase inhibitors. duration group (therefore, 80% were compliant). With a
Michael Gnant presented an update of ABCSG-12 mean follow-up since randomization of about 4.2 years
Bone Substudy at 5 yrs after diagnosis (2 years after the per woman, the annual rate of recurrence was 2.9% per
end of adjuvant therapy). This study included 1801 year in the longer-duration group, compared with 3.4%
premenopausal ER+ women, Stage I and II, with less per year in the shorter-duration group, a significant dif-
than 10 positive nodes, no chemotherapy except neoad-
ference (ratio, 0.87). The respective annual rates of juvant. All patients received ovarian ablation with breast cancer mortality were 1.4% and 1.5% per year, a goserelin and were randomized to receive tamoxifen, nonsignificant difference (ratio, 0.89). Endometrial tamoxifen + zoledronic acid 4 mg twice/year, anastra- cancer is more common with longer tamoxifen use but zole or anastrazole + zoledronic acid 4 mg twice/year. is seldom fatal. "We are preventing something like 100 1533 bone mineral density (BMD) measurements in breast cancer recurrences at the same time as causing 404 patients were centrally reviewed. Their results something like 20 endometrial cancer cases," the author showed that ovarian ablation plus tamoxifen or anastra- zole causes significant bone loss in premenopausal He also commented that earlier concerns that women (-11.3% on average). Treatment-induced bone longer tamoxifen use may, in fact, increase the risk of loss was particularly pronounced with anastrazole (- recurrence were based only on interim findings of two 14% at 3 yrs, -8% at 5 yrs). At 5 yrs, less than 50% of smaller trials. patients have regained normal BMD. Treatment- John F. Forbes presented updated results from
induced bone loss can be prevented by zoledronic acid the ATAC (Arimidex, Tamoxifen, Alone or in Combi-twice/yr. Patients receiving ZA had improved BMD at nation) study al the 100 months median follow-up. 5 yrs (+4% compared to baseline. Their results show that the effects of anastrozole in de- Adam Brufski updated the analysis of the Z-
creasing the risk of recurrence continue even after pa- FAST study at a follow-up of 36 months. This trial ran- domised patients receiving adjuvant letrozole to receive The study evaluated 5 years of primary adju- either upfront or delayed-start zoledronic acid (4 mg in- vant therapy with an aromatase inhibitor or tamoxifen travenously every 6 months). The delayed group re- in 6241 postmenopausal women. At median follow-up ceived zoledronic acid when lumbar spine (LS) or total times of 33 and 68 months, anastrozole was more effec-hip (TH) T score decreased to less than –2.0 or when a tive, had fewer serious side effects, and was better tol-nontraumatic fracture occurred. The primary end point erated than tamoxifen during active treatment. of this study was to compare the change in LS BMD at The question remained whether efficacy bene- month 12 between the groups. Secondary end points in- fits or side effects would persist after treatment comple- cluded change in TH BMD and changes in serum bone tion. This question was answered in the update pre- turnover markers at month 12. Upfront administration sented, which was based on data collected at 100 of ZA (4 mg IV every 6 months) was effective in pre- months, or approximately 9 years, some 3 or more A. Eniu: 30th Charles A. Coltman San Antonio Breast Cancer Symposium years after patients had completed their treatment. This recurrence in 313 patients with primary, lymph-node-amounts to 46,292 patient-years of data. negative breast cancer who did not receive any neoad- At 9 years, anastrozole demonstrated a signifi- juvant or adjuvant systemic therapy. Median follow-up cant advantage in terms of disease-free survival, time to was 8.5 years. Among the 200 patients in the training recurrence, time to distant recurrence, and incidence of set, analyses identified an 81-gene copy number signa-new contralateral breast cancers. Furthermore, side ef- ture (CNS) predictive of distant recurrence, much like a fects associated with the drug had diminished. previously identified 76-gene gene expression signature The reported hazard ratios (favoring anastrazole (GES). Among the 113 patients in the validation set, when compared with patients who had a good CNS, • disease-free survival, 0.85 (P = .003); those with a poor CNS were significantly more likely to • time to recurrence, 0.76 (P = .0001); develop metastases (hazard ratio, 2.8). Moreover, 5- • time to distant recurrence, 0.84 (P = .022); year metastasis-free survival was 90% with both good • contralateral breast cancer, 0.60 (P = .004). CNS and good GES, 63% with good CNS but poor Deaths after recurrence were the same at 11% GES, and 33% with poor CNS and poor GES. In multi- to 12%, as were deaths from all causes, at 20% per arm. variate analyses including conventional risk factors, pa-Recurrence rates at 5 years were 12.5% on tamoxifen tients with a poor CNS-GES combination versus a good and 9.7% on anastrozole, for a 2.8% absolute reduction. one had a significantly higher risk of metastasis (hazard At 9 years, they were 21.8% versus 17.0%, for a 4.8% ratio, 4.9). Finally, using data from separate studies test-absolute reduction. This is the first demonstration of a ing different chemotherapy regimens, the investigators carry-over effect with an aromatase inhibitor, and it is found that poor prognosis as predicted by the two sig-significantly larger for anastrazole than tamoxifen. With natures appeared to be associated with greater sensitiv-a longer follow-up, the differences have also widened ity to doxorubicin, topotecan (Hycamtin), and eto-in time to distance recurrence and in incidence of con- poside, but greater resistance to cyclophosphamide, pa- tralateral breast cancer. Contralateral breast cancers de- veloped in 4.2% on tamoxifen and 2.5% on anastrazole. C. Kent Osborne presented an overview of the
While the annual rate of fractures was ap- HER network signaling, that provides proliferation and proximately 50% higher with anastrazole during active survival signals to a subset of breast tumors. treatment, they became similar with longer follow-up, To activate the HER signaling pathway, the based on fractures in approximately 145 patients per four receptors of the network – HER1, HER2, HER3, arm. Endometrial cancers also occurred less often with and HER4 – must partner with each other, i.e. perform anastrazole off-treatment, in 4 patients versus 12 on ta- dimerization. This process ultimately results in cell pro- liferation, migration, differentiation, and apoptosis. HER2 is the favored heterodimer member, though the nostic and predictive information for individual patients other receptors are also important and must be blocked with breast cancer, thereby helping to guide treatment for optimal antitumor effect. Trastuzumab binds to the decisions, according to data from a pair of studies pre- external domain of HER2 and somehow blocks this sented. In the first study, Joe W. Gray and colleagues pathway, but it is a weak blocker of signals from other
identified six genes whose levels of transcription were dimer pairs. While trastuzumab is beneficial in about
associated with a response to lapatinib in vitro. Expres-
50% of patients in the adjuvant setting, de novo resis- sion of the genes can be easily measured in a single tance is common and acquired resistance is universal. paraffin section with a technique called the branch cap- This could be due to activation of some other aspect of ture assay. The investigators assessed the 6-gene signa- the redundant survival pathway or reactivation of the ture clinically using tissue and data from the EGF30001 HER pathway.Resistance to trastuzumab develops by randomized trial. Among HER2-positive patients, the multiple mechanisms: risk of breast cancer progression was marginally re- duced with paclitaxel-lapatinib therapy for patients pre- • the presence of mucin, which interferes with dicted to be sensitive to lapatinib by the signature, the binding of trastuzumab; compared with their counterparts predicted to not be • mutations in HER2, especially loss of the ex- sensitive (hazard ratio, 0.58). In contrast, the signature ternal binding domain; was not useful for risk stratification among HER2- • overloading of growth factors that cause negative patients treated with paclitaxel-lapatinib. ligands to flood the system and overcome the block; In the second study, John A. Foekens, and
• activation of a redundant survival pathway, coinvestigators assessed genomic predictors of distant such as the estrogen receptor; Journal of Radiotherapy & Medical Oncology, March 2008 Vol. XIV No. 1:54-59 • presence in the membrane of other kinases 1 of a 21-day cycle. For these triple-negative patients, progression-free survival was prolonged to 4.1 months Combining receptor inhibitors with each other, with the combination, compared with 2.1 months with or with downstream/alternative signaling inhibitors, capecitabine alone, for a 32% reduction in risk. Overall may overcome these roadblocks. New agents that may response rates also increased with the combination, to meet this aim include the tyrosine kinase inhibitors la- 27% from 9% with monotherapy. The differences be- patinib, gefitinib, and erlotinib and the dimerization in- tween the arms reflected those observed in the larger hibitor pertuzumab (investigational). These are not ef- population, though outcomes were better overall in the fective by themselves, however, since each leaves a part non-triple-negative group. The combination was rela-of the pathway "open," but they are powerful when tively well tolerated. The most common grade 3 or 4 grouped together in a way which more completely adverse events were neutropenia (68%) and peripheral blocks signals from all heterodimer pairs. sensory neuropathy (21%). Both were manageable . Observations in preclinical models have found Laura Esserman presented, on behalf of Nora
this approach to have a powerful effect. Cocktails of Hylton, the I-SPY multi-institutional study of locally
these agents have been shown to completely eradicate advanced breast cancer integrating serial biopsy and
some xenograft models of human breast cancer. The es-
MRI to measure response of tumors to neoadjuvant trogen receptor must be blocked, either with tamoxifen chemotherapy. The primary objective is to identify sur-or ideally with aromatase inhibitors, which completely rogate markers of response that are predictive of patho-deprive the tumor of estrogen. logic complete response (pCR) and survival in women There have been no clinical trials yet of such with stage II and III breast cancer. The findings should combinations in untreated patients, though they are on enable clinicians someday to identify nonresponders the horizon. Forthcoming studies will evaluate numer- early and design effective therapies for them. The data ous combinations of lapatinib and trastuzumab with and set will eventually be available to the public in the form without paclitaxel in the neoadjuvant and adjuvant set- of an integrative and clinically useful portal. The trial tings, and the combination of pertuzumab, trastuzumab, accrued 237 patients from nine centers. Patients under-and erlotinib in the metastatic setting. went an anthracycline-based neoadjuvant regimen and Hope Rugo presented results showing that the
had serial MRI and core biopsies performed at baseline, combination of capecitabine (Xeloda) and ixabepilone after one cycle, during treatment, and before surgery to (Ixempra) appears to be active in patients with the tri- identify markers of tumor response. In the current ple-negative breast cancer phenotype. In heavily pre- analysis of 222 patients, mean age was 49 and median treated metastatic breast cancer patients, the regimen tumor size was 6 cm. Seventy percent had positive yielded an overall response rate of 27% and median nodes, 54% were estrogen receptor (ER)-positive, 28% progression-free survival of 4.1 months, according to a had HER2 overexpression, 38% had intermediate-grade subset analysis of 187 patients from a larger random- lesions, and 39% had high-grade lesions. Patients were ized phase III trial of capecitabine with and without ix- younger, tended to have more ER– disease (45%), and abepilone. The author pointed out that "triple-negative" tended to be HER+ (27%). Few patients had favorable breast cancers -- those that are estrogen receptor- recurrence scores or prognoses, according to clinical negative, progesterone receptor-negative, and HER2- prognostic tools. Distribution of molecular subtypes by negative -- are associated with an aggressive phenotype 161 cDNA showed the tumors to be luminal A (27%), and poor prognosis as a result of their increased mitotic luminal B (21%), HER2 (9%), basal (35%), and normal index, central necrosis, proportion of apoptotic cells, (8%). Interestingly, basal tumors had a pCR rate of and other high-risk pathological features. Patients with 45%, while luminal A had a pCR rate of 0%. The over-triple-negative tumors develop their disease at an earlier all pCR rate was 27%, and 84% of these patients also age, are more likely to relapse, and tend to develop vis- had a pCR in the lymph nodes. By HER2 and ER ceral and brain metastases as well as bone metastases, status, pCR rates were 28.1% in HER2+/ER+ patients, compared with other breast cancer subtypes. The study 48.1% in HER2+/ER– patients (without trastuzumab), population was part of a prospective multicenter phase 9.6% in HER2–/ER+ patients, and 35.7% in HER2–III trial of 752 women with metastatic breast cancer re- /ER– patients. MRI characterized the imaging pattern of sistant to taxanes and pretreated with or resistant to an- the tumors as unicentric mass and well-defined margins thracyclines. Patients were randomized to capecitabine (17%), multilobulated mass and well-defined margins monotherapy 1250 mg/m2 twice daily on days 1 to 14 (30%), area enhancement and irregular margins (nod-of a 21-day cycle, or to capecitabine 1000 mg/m2 twice ules) (31%), area enhancement and irregular margins daily on days 1 to 14 plus ixabepilone 40 mg/m2 on day (no nodes) (14%), and spectral spreading (9%). Change A. Eniu: 30th Charles A. Coltman San Antonio Breast Cancer Symposium in MRI volume proved to be the optimal imaging lymphovascular invasion, and HER2 positivity. In con-measure of tumor response. By MRI phenotype, breast- trast, age, type of biopsy, histologic grade, and hor- conserving therapy was most feasible in types 1 and 2. mone-receptor status were not associated with this out-Investigators determined that residual cancer burden come. In a multivariate analysis among Group 1 pa-(RCB) may be a better method of assessing response tients, the odds of having positive non-sentinel nodes in-than pCR. RCB integrates several pathologic features, creased significantly with increasing number of positive including lymph node status, extent of tumor bed, tu- sentinel nodes (odds ratio, 2.01), larger clinical tumor mor size, and tumor cellularity. Output is a continuous size (1.22), and the presence of lymphovascular invasion measure (RCB 0 vs 1 vs 2 vs 3) rather than a dichoto- (1.88). Odds decreased significantly with increasing mous "yes or no" measure, the authors concluded. By number of sentinel nodes examined (0.73) and increas-pCR and RCB, I-SPY validated molecular predictors of ing number of hot spots (0.56). Similarly, in a multivari-response that clinicians are accustomed to using. The ate analysis among Group 2 patients, the odds of having most highly predictive were ER and phosphorylated positive non-sentinel nodes increased significantly with ER, HER2 and phosphorylated HER2, the Netherlands increasing number of positive sentinel nodes (odds ratio, Cancer Institute 70-gene set, and the OncotypeDX re- 2.12), larger clinical tumor size (1.22), and the presence of lymphovascular invasion (1.88). Odds decreased sig- Thomas B. Julian and colleagues with the Na-
nificantly with increasing number of sentinel nodes ex- tional Surgical Adjuvant Breast and Bowel Project ana- amined (0.73) and increasing number of hot spots lyzed data from the NSABP B-32 randomized trial, in (0.56). Combinations of these factors identified subsets which women with breast cancer and clinically negative of patients who had a less than 20% probability of hav-axillary nodes underwent sentinel node resection (using ing positive non-sentinel lymph nodes. In particular, a combination of isotope, dye, and palpation) always Group 2 patients who had one hot spot, no lymphovas-followed by axillary dissection (Group 1) or followed by cular invasion, a single positive sentinel node, and five axillary dissection only when the sentinel node was sentinel nodes examined had probabilities of roughly positive, as determined by hematoxylin and eosin stain- 5% to 15%, depending on clinical tumor size. ing (H&E) (Group 2). Analyses were based on the 1166 The authors conclude that some breast cancer patients overall who had a positive sentinel node, un- patients with positive sentinel lymph nodes have factors derwent axillary dissection, and had complete data. In associated with a low probability of having any other univariate analysis, the factors associated with a higher positive nodes and may therefore be able to safely skip rate of positive non-sentinel nodes were study group completion axillary dissection, such as patients who (Group 2), fewer sentinel nodes examined, fewer hot have very small tumors, no lymphovascular invasion, spots, more positive sentinel nodes, larger clinical tumor and only a single positive sentinel node out of multiple size, primary tumor location in the upper outer quadrant, nodes.


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