Adjuvant Systemic Therapy For Women Research Articles

Prognostic role of the stromal tumor-infiltrating lymphocytes (TILs) in women with early ER+/HER2+ breast cancer (BC) in whom adjuvant chemotherapy (ChT) was omitted.

e12526 Background: Adjuvant systemic therapy in women with early ER+/HER2+ BC usually includes ChT, trastuzumab (T) and endocrine therapy (ET). High level of TILs is associated with better outcome in HER2+ disease. Here we explore the outcome and prognostic role of TILs in women with early ER+/HER2+ BC in whom ChT was omitted. Methods: Women with ER+ (IHC ≥ 1%) and HER2+ (IHC3+ and/or FISH ratio ≥ 2.0) early BC who underwent surgery between years 2006 and 2016 at the Institute of Oncology Ljubljana and did not receive adjuvant ChT were eligible for this study. Hematoxilin and eosin slides of primary tumors were retrieved and evaluated for the percentage of stromal TILs. Distant disease-free survival (DDFS) was estimated by the Kaplan-Meier method. The association between DDFS and TILs level was explored in the Cox proportional hazard model. Relative survival was used for estimating the probability of dying due to the breast cancer or other causes. Results: During the 10-year period 86 (29.4%) out of 292 women with early ER+/HER2+ BC who underwent surgery did not receive adjuvant ChT. ChT was omitted due to the stage I disease (n=30), comorbidities (n=25), older age (n=19), refusal of treatment (n=9) and other causes (n=3). Five (5.8%) and 81 (94.1%) women received T and ET, respectively. Their median age was 65.8 yrs (IQR 55.7, 75.6 yrs) and 45 (52.3%) had stage I disease. There were 53 (61.6%), 24 (27.9%) and 9 (10.4%) women with low (<10%), intermediate (≤10% to <40%) and high (≥ 40%) level of TILs, respectively. After median follow-up of 10 years 28 events (distant recurrence or death) occurred. The 10-year DDFS for those who did not receive ChT due to the stage I disease, comorbidities and older age was 91% (95% CI, 0.79 to 1.00), 38% (95% CI, 0.18 to 0.75]) and 26% (95% CI, 0.10 to 0.66) (p˂0.0001), respectively. After excluding women with stage I disease the estimated probability of dying due to the breast cancer and due to other causes was 26.7% and 26.5%, respectively. Overall, for every 10% increase in TILs the risk of distant recurrence or death was reduced for 18% (HR=0.82; 95% CI, 0.64 to 1.05) (p=0.11). In the multivariable Cox model, higher TILs level was a significant predictor of better DDFS (HR 0.75; 95% CI, 0.57 to 0.98) (p=0.041) (Table). Conclusions: Women with stage I ER+/HER2+ BC who do not receive adjuvant ChT and T but do receive adjuvant ET may still have a very good outcome. In contrast, survival of women who do not receive adjuvant ChT and T for other reasons is poor; however, only a half of those deaths are related to BC. TIL is a favourable prognostic biomarker which might be helpful when de-escalation of systemic therapy in women with ER+/HER2+ BC is considered.[Table: see text]

Neoadjuvant and Adjuvant Systemic Therapy for Newly Diagnosed Stage II-IV Epithelial Ovary, Fallopian Tube, or Primary Peritoneal Carcinoma: A Practice Guideline.

Background: This study aims to provide guidance for the use of neoadjuvant and adjuvant systemic therapy in women with newly diagnosed stage II–IV epithelial ovary, fallopian tube, or primary peritoneal carcinoma. Methods: EMBASE, MEDLINE, and Cochrane Library were investigated for relevant systematic reviews and phase III trials. Articles focusing on consolidation and maintenance therapies were excluded. Results: For women with potentially resectable disease, primary cytoreductive surgery, followed by six to eight cycles of intravenous three-weekly paclitaxel and carboplatin is recommended. For those with a high-risk profile for primary cytoreductive surgery, neoadjuvant chemotherapy can be an option. Adjuvant chemotherapy with six cycles of dose-dense weekly paclitaxel plus three-weekly carboplatin can be considered for women of Japanese descent. In women with stage III or IV disease, the incorporation of bevacizumab concurrent with paclitaxel and carboplatin is not recommended for use as adjuvant therapy unless bevacizumab is continued as maintenance therapy. Intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel can be considered for stage III optimally debulked women who did not receive neoadjuvant chemotherapy. However, intraperitoneal administration of chemotherapy with bevacizumab should not be considered as an option for stage II–IV optimally debulked women. Discussion: The recommendations represent a current standard of care that is feasible to implement and valued by both clinicians and patients.

143P The impact of de-escalation of adjuvant systemic therapy on the outcome of women with early ER+/HER2+ breast cancer

Adjuvant systemic therapy in women with early ER+/HER2+ breast cancer includes chemotherapy (ChT), one year of anti-HER2 therapy and at least five years of hormonal therapy (HT). Here, we explore the impact of de-escalation of adjuvant therapy on the outcome in women with early ER+/HER2+ breast cancer.

Abstract P2-18-06: Value of PAM50 risk of recurrence score in patients with HR positive HER2 negative early breast cancer and intermediate risk: A single cancer center institution prospective observational study

Abstract Background: Currently, clinico-pathological characteristics (CPC) such as tumor size, lymph node status, tumor grade, proliferation, lympho-vascular invasion and percentage of cells expressing estrogen (ER) and progesterone receptors (PR) are usually considered in order to guide decisions on adjuvant systemic therapy for women with early-stage breast cancer (EBC). The indication of adjuvant chemotherapy (ACT) or not is relatively easy in women with ER+/HER2- EBC with either poor or very good CPC. However, this decision is much more difficult in those with intermediate CPC (essentially defined by grade II tumor with low PR expression and/or intermediate proliferation). The PAM50-based Prosigna risk of recurrence (ROR) is one of the multigene assays that have been evaluated and recommended for guiding treatment decision. We report here our experience on the impact of ROR in treatment decision-making in women with intermediate CPC. Patients and methods: Between March 2016 and May 2019, ROR was performed in 200 consecutive women with intermediate CPC ER+/HER2- EBC. The clinical decision (ACT or not) was prospectively recorded before and after ROR assessment and finally after the consultation with each patient. Data were summarized by frequency and percentage for categorical variables and by median and range for continuous variables. Associations between variables will be assessed using Chi-square or Fisher’s exact test for qualitative variables and the Mann-Whitney for continuous variables. All reported p-values were two-sided. For all statistical tests, differences were considered significant at the 5% level. Statistical analysis was performed using STATA v13 software. Results: Median age at diagnostic was 57 years [30-79] and 119 (59.5%) were post-menopausal. Median tumor size was 18mm [8-70mm]. Most tumors were PR+ (n=153, 76.5%), no special type (NST) carcinomas (n=172, 86%), Elston and Ellis grade II (n=183, 91.5%), with Ki67 value between 10 and 20 % (n=117, 62.6%). Lympho vascular invasion was observed in 38 tumors (19%), 124 patients were pN0 (62%), 20 pNmi (10%) and 55 pN1a (27.5%). Using the immunohistochemical (IHC)-based definition proposed by Prat et al. (JCO 2013), 90 tumors were luminal A (45%) and 110 luminal B (55%). There was 59.5% of concordance between IHC subtype classification and PAM50. ROR distribution was as follows: ROR-low (n=33; 16.5%); ROR-intermediate (n=75; 37.5%); and ROR-high (n=92; 46%). The clinical decision of modalities of adjuvant medical therapy switched after ROR assessment for 74 patients (37%): -26 patients from ACT plus endocrine therapy (ET) to ET only (13%); 9 and 17 have respectively a ROR-low or -intermediate and 23 a luminal A tumor according to PAM50, -48 patients from ET only to ACT plus ET (24%); 7 and 41 have respectively a ROR-intermediate or high and 44 a luminal B tumor. Importantly, 8 of them don’t received ACT at the issue of the consultation with the medical oncologist. Conclusion: In our experience, the use of ROR leads us more often to escalate than de-escalate adjuvant therapy, proving that the definition of the group with intermediate prognosis remains uncertain and variable according medical teams. Citation Format: Vincent Nicolaï, Julia Gilhodes, Jean Louis Lacaze, Mony Ung, Eleonora De Maio, Raphaelle Duprez-Paumier, Charlotte Vaysse, Thomas Filleron, Eva Jouve, Gabrielles Selmes, Camille Franchet, Carole Massabeau, Cyprian Chira, Francoise Izar, Henri Roché, Anne Pradines, Florence Dalenc. Value of PAM50 risk of recurrence score in patients with HR positive HER2 negative early breast cancer and intermediate risk: A single cancer center institution prospective observational study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-18-06.

202P - Adjuvant systemic therapy in women with early breast cancer and intermediate prosigna ROR scores: Is chemotherapy use declining? Evidence from a large practice

BackgroundDecision making on adjuvant systemic therapy in women with primary node-negative, HR+ breast cancer and intermediate risk scores on a molecular tumor profile has often been difficult, and may be based also on additional clinical factors such as age, tumor size and grade. In mid-2018 new level 1 evidence on the lack of additional benefit with chemo-hormonal therapy versus hormonal therapy for most of these patients emerged. We sought to determine if systemic adjuvant therapy choices have changed in a large community practice of over 200 medical oncologists in the U.S. using in-house tumor testing with the Prosigna PAM 50 assay. There is robust clinical evidence on recurrence risk estimation with PAM 50. Data from the ABCSG-8 estimates distant RFS of 91.3% at ten years in the intermediate risk group treated with hormonal therapy alone. Decreased chemo use would lead to decreased therapy-related toxicity and probable healthcare cost savings. MethodsWe compared Prosigna ROR results in individual postmenopausal women with HR+, node- primary breast cancers from the period 9/17 through 6/18, with the period 6/18 through 3/19. Approximately 800 total tests were run from one large practice in the U.S. About 20% fell into the intermediate score range We compared the number of patients receiving adjuvant chemohormonal therapy versus hormonal therapy alone or no systemic therapy. Physicians were polled as to whether their decisions were influenced by the ROR score, clinical factors, or both. ResultsDuring the period studied, the percentage of patients with intermediate ROR scores receiving adjuvant therapy declined. Physicians based their decisions on the scores primarily, along with other clinical factors. The percentages of physicians influenced by each factor and the totals for each category of treatment will be presented in the final poster. ConclusionsOncologists in a large practice are influenced in making breast cancer adjuvant therapy decisons by recent trial data, as well as clinical factors, and may extrapolate from one molecular profile to another. Adjuvant chemo use in HR+ node- patients is likely to remained confined to patients with a high-risk profile, regardless of the assay used. Legal entity responsible for the studyFlorida Cancer Specialists. FundingHas not received any funding. DisclosureL.L. Hart: Advisory / Consultancy, Travel / Accommodation / Expenses: Self. All other authors have declared no conflicts of interest.

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update Summary

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update Summary

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: ASCO Clinical Practice Guideline Update—Integration of Results From TAILORx

This focused update addresses the use of Oncotype DX in guiding decisions on the use of adjuvant systemic therapy. ASCO uses a signals approach to facilitate guideline updating. For this focused update, the publication of the Trial Assigning Individualized Options for Treatment (TAILORx) evaluating noninferiority of endocrine therapy alone versus chemoendocrine therapy for invasive disease-free survival in women with Oncotype DX scores provided a signal. An expert panel reviewed the results of TAILORx along with other published literature on the Oncotype DX assay to assess for evidence of clinical utility. For patients with hormone receptor-positive, axillary node-negative breast cancer whose tumors have Oncotype DX recurrence scores of less than 26, there is little to no benefit from chemotherapy, especially for patients older than age 50 years. Clinicians may recommend endocrine therapy alone for women older than age 50 years. For patients 50 years of age or younger with recurrence scores of 16 to 25, clinicians may offer chemoendocrine therapy. Patients with recurrence scores greater than 30 should be considered candidates for chemoendocrine therapy. Based on informal consensus, the panel recommends that oncologists may offer chemoendocrine therapy to these patients with recurrence scores of 26 to 30. Additional information can be found at www.asco.org/breast-cancer-guidelines.

Practical consensus recommendations on duration of adjuvant hormonal therapy in breast cancer.

Optimization of adjuvant systemic therapy in women with early-stage hormone receptor-positive breast cancer includes the consideration of chemotherapy and duration of hormone therapy. Adjuvant hormonal therapy significantly improves long-term survival of breast cancer patients with hormone receptor-positive disease. Despite the proven clinical efficacy of tamoxifen and aromatase inhibitors, many breast cancer survivors either fail to take the correct dosage at the prescribed frequency (adherence) or discontinue therapy (persistence). Expert oncologist discussed on the duration of adjuvant hormonal therapy for improvement of OS and quality of life of breast cancer patients by providing reduction in recurrence and mortality. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Focused Update Guideline Summary.

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Focused Update Guideline Summary.

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Focused Update.

Purpose This focused update addresses the use of MammaPrint (Agendia, Irvine, CA) to guide decisions on the use of adjuvant systemic therapy. Methods ASCO uses a signals approach to facilitate guideline updates. For this focused update, the publication of the phase III randomized MINDACT (Microarray in Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy) study to evaluate the MammaPrint assay in 6,693 women with early-stage breast cancer provided a signal. An expert panel reviewed the results of the MINDACT study along with other published literature on the MammaPrint assay to assess for evidence of clinical utility. Recommendations If a patient has hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-negative breast cancer, the MammaPrint assay may be used in those with high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy due to its ability to identify a good-prognosis population with potentially limited chemotherapy benefit. Women in the low clinical risk category did not benefit from chemotherapy regardless of genomic MammaPrint risk group. Therefore, the MammaPrint assay does not have clinical utility in such patients. If a patient has hormone receptor-positive, HER2-negative, node-positive breast cancer, the MammaPrint assay may be used in patients with one to three positive nodes and a high clinical risk to inform decisions on withholding adjuvant systemic chemotherapy. However, such patients should be informed that a benefit from chemotherapy cannot be excluded, particularly in patients with greater than one involved lymph node. The clinician should not use the MammaPrint assay to guide decisions on adjuvant systemic therapy in patients with hormone receptor-positive, HER2-negative, node-positive breast cancer at low clinical risk, nor any patient with HER2-positive or triple-negative breast cancer, because of the lack of definitive data in these populations. Additional information can be found at www.asco.org/breast-cancer-guidelines and www.asco.org/guidelineswiki .

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Summary.

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline Summary.

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline.

To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer. A literature search and prospectively defined study selection sought systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies, and prospective comparative observational studies published from 2006 through 2014. Outcomes of interest included overall survival and disease-free or recurrence-free survival. Expert panel members used informal consensus to develop evidence-based guideline recommendations. The literature search identified 50 relevant studies. One randomized clinical trial and 18 prospective-retrospective studies were found to have evaluated the clinical utility, as defined by the guideline, of specific biomarkers for guiding decisions on the need for adjuvant systemic therapy. No studies that met guideline criteria for clinical utility were found to guide choice of specific treatments or regimens. In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2, the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer. No biomarker except for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens. Treatment decisions should also consider disease stage, comorbidities, and patient preferences.

Adverse prognostic value of peritumoral vascular invasion: is it abrogated by adequate endocrine adjuvant therapy? Results from two International Breast Cancer Study Group randomized trials of chemoendocrine adjuvant therapy for early breast cancer

BackgroundPeritumoral vascular invasion (PVI) may assist in assigning optimal adjuvant systemic therapy for women with early breast cancer. Patients and methodsPatients participated in two International Breast Cancer Study Group randomized trials testing chemoendocrine adjuvant therapies in premenopausal (trial VIII) or postmenopausal (trial IX) node-negative breast cancer. PVI was assessed by institutional pathologists and/or central review on hematoxylin–eosin-stained slides in 99% of patients (analysis cohort 2754 patients, median follow-up >9 years). ResultsPVI, present in 23% of the tumors, was associated with higher grade tumors and larger tumor size (trial IX only). Presence of PVI increased locoregional and distant recurrence and was significantly associated with poorer disease-free survival. The adverse prognostic impact of PVI in trial VIII was limited to premenopausal patients with endocrine-responsive tumors randomized to therapies not containing goserelin, and conversely the beneficial effect of goserelin was limited to patients whose tumors showed PVI. In trial IX, all patients received tamoxifen: the adverse prognostic impact of PVI was limited to patients with receptor-negative tumors regardless of chemotherapy. ConclusionAdequate endocrine adjuvant therapy appears to abrogate the adverse impact of PVI in node-negative disease, while PVI may identify patients who will benefit particularly from adjuvant therapy.

Is information from axillary dissection relevant to patients with clinically node-negative breast cancer?

The changing trends in the diagnosis and management of women with invasive breast cancer have prompted an examination of the need for routine axillary lymph node dissection (ALND) in women with a clinically negative axilla. The objective of this study was to examine the value of information from an ALND in guiding the selection of adjuvant systemic therapy for women with clinically node-negative breast cancer. Between January 1996 and June 2000, 447 clinically node-negative women underwent an ALND as part of their treatment for invasive breast cancer at Westmead Hospital. Three categories of risk of recurrence were devised, based on the primary tumor characteristics alone, without information from an ALND. Recommendations for adjuvant systemic therapy with and without information from an ALND were compared, and the frequency of change was calculated. Overall, 12% of women had their treatment recommendation altered by their pathologic nodal status based on the model treatment algorithm. For women in the low-risk category (pathologic tumor size </=10 mm, grade 1, lymphovascular invasion [LVI] negative, and estrogen receptor [ER] positive), 17% of those less than 50 years old and 14% of those 50-69 years old would have a shift in their treatment recommendations based on the pathologic nodal status. In addition, 13% of the women less than 50 years old and 10% of those 50-69 years old were recommended for more intensive chemotherapy on the basis of four or more involved nodes. For women in the high-risk category (pathologic tumor size greater than 20 mm or greater than 10 mm associated with any unfavorable prognostic factor [grade 3, LVI, or negative ER]), 19% of those less than 50 years old and 18% of those 50-69 years old were recommended for more intensive chemotherapy. Information from ALND did not alter the treatment recommendation for women >/=70 years old, as they were not recommended chemotherapy in the model algorithm. If women >/=70 years old who were node positive and had an ER-negative tumor were recommended chemotherapy, 14% in the high-risk category would have had their treatment recommendation altered as a result of the information from ALND. The continued utilization of ALND is appropriate in women less than 70 years old in the high-risk category. In other patients less than 70 years old, the pathologic nodal status is of value in guiding the selection of women for adjuvant systemic therapy. For women >/=70 years old, information from an ALND adds little to the selection of patients for adjuvant systemic therapy. However, in selected patients >/=70 years old who are classified as high risk on the basis of unfavorable primary tumor features, and are potential candidates for chemotherapy, an ALND would be appropriate.

The use of gonadotrophin-releasing hormone (GnRH) agonists in early and advanced breast cancer in pre- and perimenopausal women

Gonadotrophin-releasing hormone (GnRH) agonists, in particular goserelin (‘Zoladex’), are increasingly being used for the treatment of breast cancer in women with functioning ovaries. They act by downregulating pituitary GnRH receptors, thereby suppressing the release of luteinising hormone (LH) and follicle stimulating hormone (FSH), which, in turn, reduce the main source of oestradiol production in the ovaries. GnRH agonists have been shown to be as effective therapeutically as surgical ovarian ablation in pre- and perimenopausal women with advanced breast cancer. The combination of a GnRH agonist such as goserelin with the peripheral oestrogen antagonist, tamoxifen, may be used to produce ‘combined oestrogen blockade’. In advanced breast cancer, this regimen prolongs progression-free survival and increases both the response rate and duration relative to the use of a GnRH agonist alone. In patients with early breast cancer, the addition of goserelin to ‘standard treatment’ (i.e. surgery±tamoxifen, chemotherapy or radiotherapy) results in a significant benefit in recurrence-free survival and overall survival. This benefit was most apparent in patients with oestrogen receptor (ER) +ve tumours. Goserelin, when used either alone or in combination with tamoxifen as an adjuvant systemic therapy in women with ER +ve tumours, has been shown in clinical trials to produce recurrence-free survival rates equivalent to cytotoxic chemotherapy such as cyclophosphamide, methotrexate, 5-fluorouracil (CMF). Evidence suggests that at least part of the effect of adjuvant cytotoxic chemotherapy in premenopausal women is produced by ovarian ablation. Endocrine therapy with goserelin or goserelin plus tamoxifen should now be considered a treatment option in the management of premenopausal women with ER +ve early breast cancer.

Adjuvant systemic therapy for lymph node-negative breast cancer less than or equal to 1 cm.

Routine screening mammography has increased the incidence of stage I breast cancers. Many more women are being diagnosed with lymph node-negative tumors that are less than or equal to 1 cm in greatest diameter. The National Surgical Adjuvant Breast and Bowel Project recently performed a retrospective analysis of 10,302 women participating in one of five clinical trials, including women with lymph node-negative breast cancer. Of these women, 1259 had tumors less than or equal to 1 cm. The analysis of the women with tumors less than or equal to 1 cm revealed an improved relapse-free survival (RFS) if tamoxifen was given after surgery, compared with surgery alone, for women with estrogen receptor (ER)-positive tumors; and for women with ER-negative tumors, RFS was improved by delivering chemotherapy after surgery. The authors suggested that adjuvant systemic therapy should be considered for anyone with an invasive breast cancer, regardless of the size of the tumor. This paper reviews the data presented in that important, historic article, and discusses their conclusions. Also reviewed are the most recent recommendations for treatment of primary breast cancer from the International Consensus Panel that convened at the Seventh International Conference on Adjuvant Therapy of Primary Breast Cancer in St. Gallen, Switzerland. That panel also addressed the issue of adjuvant systemic therapy in women considered to have a minimal or low risk of developing recurrent disease.

Use of the St Gallen classification for patients with node-negative breast cancer may lead to overuse of adjuvant chemotherapy.

The 1998 St Gallen classification was devised to guide clinicians in the use of adjuvant systemic therapy for women with early breast cancer. In this study, the classification was applied to a historical group of patients with node-negative breast cancer who were treated without adjuvant therapy. The St Gallen classification was applied to 421 women with breast cancer treated with conservative surgery and radiotherapy alone between 1979 and 1994. Primary tumour characteristics were reviewed centrally. When the most stringent version of the St Gallen classification was applied (grade 2 or 3 tumours classified as "high risk"), only 10 per cent of patients were "low risk", with a 10-year distant relapse-free survival (DRFS) rate of 100 per cent, and 15 per cent were at "intermediate risk" (10-year DRFS rate of 94 per cent). The high-risk group (75 per cent of women) had a 10-year DRFS rate of 77 per cent (P < 0.01). If the St Gallen classification had been applied to all patients in this series who were aged less than 70 years, up to 91 per cent would have been recommended to have chemotherapy. The St Gallen classification is an inaccurate measure of prognosis for patients with node-negative breast cancer and should be used with caution.

Adjuvant systemic therapy in women with early-stage breast cancer at high risk for relapse.

Adjuvant systemic therapy in women with early-stage breast cancer at high risk for relapse.

Systemic Adjuvant Therapy in Women With Resected Node-Negative Breast Cancer

Currently, the role of adjuvant systemic therapy in women with node-negative breast cancer is being determined. Several studies of adjuvant hormonal therapy and adjuvant chemotherapy have demonstrated a moderate reduction in the risk of recurrence in the treated patients. With relatively limited follow-up, however, overall survival has not improved with use of adjuvant therapy. The use of prognostic factors to select those patients at highest risk for relapse is an active area of oncologic research. The decision to recommend adjuvant therapy necessitates assessment of the probability of recurrence, the expected reduction of risk with adjuvant therapy, the toxic effects of therapy, and the influence of treatment on the patient's overall quality of life.

Node-negative breast cancer: prognostic subgroups defined by tumor size and flow cytometry.

Adjuvant systemic therapy for women with node-negative breast cancer is most easily justified for those patients at highest risk of relapse. We have examined the impact of tumor size, histologic grade, estrogen receptor (ER) status, tumor ploidy, and S-phase fraction (SPF) on relapse-free survival (RFS) for 169 patients with node-negative breast cancer in order to identify groups of patients at high and low risk of relapse. Patients with small tumors (less than or equal to 1.0 cm) had a significantly better RFS than those with larger tumors (P = .005), with 96% remaining relapse-free at 5 years. Patients with tumors less than or equal to 1.0 cm were thus excluded from analysis when attempting to define a group with a poor prognosis. Within the group of patients with tumors greater than 1.0 cm, tumor ploidy (P = .63), ER status (P = .3), or progesterone receptor (PgR) status (P = .24) did not predict for RFS. Patients with grade 1 or 2 infiltrating ductal tumors had a significantly better prognosis than those with grade 3 tumors (P = .04). The prognostic factor that gave the widest separation between subgroups, however, was SPF. Patients whose tumors were greater than 1.0 cm with an SPF less than or equal to 10% had a 5-year RFS of 78% compared with a 5-year RFS of 52% for those with an SPF greater than 10% (P = .006). We have combined tumor size and SPF to identify three prognostic groups: (1) tumor less than or equal to 1.0 cm, 5-year RFS 96%; (2) tumor greater than 1.0 cm plus SPF less than or equal to 10%, 5-year RFS 78%; 3) tumor greater than 1.0 cm plus SPF greater than 10%, 5-year RFS 52%. These prognostic groupings may help identify patients most suitable for adjuvant therapy.