Early-stage Invasive Breast Carcinoma Research Articles

Biological effects of intraoperative radiation therapy: histopathological changes and immunomodulation in breast cancer patients.

Intraoperative radiation therapy (IORT) delivers a single accelerated radiation dose to the breast tumor bed during breast-conserving surgery (BCS). The synergistic biologic effects of simultaneous surgery and radiation remain unclear. This study explores the cellular and molecular changes induced by IORT in the tumor microenvironment and its impact on the immune response modulation. Patients with hormone receptor (HR)-positive/HER2-negative, ductal carcinoma in situ (DCIS), or early-stage invasive breast carcinoma undergoing BCS with margin re-excision were included. Histopathological evaluation and RNA-sequencing in the re-excision tissue were compared between patients with IORT (n=11) vs. non-IORT (n=11). Squamous metaplasia with atypia was exclusively identified in IORT specimens (63.6%, p=0.004), mimicking DCIS. We then identified 1,662 differentially expressed genes (875 upregulated and 787 downregulated) between IORT and non-IORT samples. Gene ontology analyses showed that IORT was associated with the enrichment of several immune response pathways, such as inflammatory response, granulocyte activation, and T-cell activation (p<0.001). When only considering normal tissue from both cohorts, IORT was associated with intrinsic apoptotic signaling, response to gamma radiation, and positive regulation of programmed cell death (p<0.001). Using the xCell algorithm, we inferred a higher abundance of γδ T-cells, dendritic cells, and monocytes in the IORT samples. IORT induces histological changes, including squamous metaplasia with atypia, and elicits molecular alterations associated with immune response and intrinsic apoptotic pathways. The increased abundance of immune-related components in breast tissue exposed to IORT suggests a potential shift towards active immunogenicity, particularly immune-desert tumors like HR-positive/HER2-negative breast cancer.

Expression of PD-L1 in Early-Stage Invasive Breast Carcinoma and Its Relation to Tumor-Infiltrating Lymphocytes.

Objectives:Immunotherapeutic targets became one of the promising approaches in breast cancer (BC), especially in advanced stage triple-negative subtype (TNBC). However, the role of programmed cell death ligand 1 (PD-L1) targeting in other BC subtypes, especially in early-stage carcinoma is less explored. We aimed in this study to investigate the prevalence of PD-L1 in early-stage invasive BC of different molecular subtypes and to elucidate its relation to tumor-infiltrating lymphocytes (TILS) density (cytotoxic and regulatory T-cells), established clinicopathological factors and patients’ outcome. Material and Methods:One hundred and nine cases of early-stage BC were enrolled in our study. Cases were classified into five molecular subtypes according to the Immunohistochemical data. PD-L1, FOXP3 and CD8 immunostaining were analyzed for all studied cases. PD-L1 expression was correlated with CD8+ cytotoxic T-cells, FOXP3+ regulatory T-cells, histopathologic parameters, BC molecular subtypes, 7-years disease-free survival (DFS) and overall survival (OS). Results:PD-L1 was expressed in 11% of the studied early-stage BC cases. It showed a significant correlation with high tumor grade (p= <0.001), development of metastasis (p=0.037), high FOXP3+ T-cell density (p= <0.001) and low CD8+ T-cells density (p= <0.001). PD-L1 expression was higher in TNBC (16.1%), followed by HER2/neu-enriched group (14.3%). All luminal A cases showed negative PD-L1 expression. PD-L1 was found to be an independent prognostic factor for patients’ survival (DFS; p=0.031 and OS: p=0.04). Conclusion:Although the impact of PD-L1 on early-stage BC outcomes had not been clearly established, our results indicated that PD-L1 is a negative prognostic marker in early settings. PD-L1 can serve as a new therapeutic target for patients with high-grade early-stage breast carcinoma.

Abstract OT1-10-01: The Breast Cancer Index registry study: A prospective multi-center observational study to evaluate patient outcome, clinical impact, and medication adherence in HR+ breast cancer patients considering treatment with extended endocrine therapy

Abstract Background: Hormone receptor-positive (HR+) is the most common molecular subtype of breast cancer accounting for approximately 2 out of every 3 patients. Adjuvant anti-estrogen therapy is the cornerstone of systemic therapy, underscoring the critical role of endocrine treatment which affects the majority of women with breast cancer. Furthering efforts to better understand endocrine response and resistance and implementing genomic tools to help individualize patient selection for endocrine therapy are of ongoing importance to improve outcomes. Breast Cancer Index (BCI) is a gene expression signature composed of the Molecular Grade Index (MGI) and HOXB13/IL17BR (H/I) that predicts the likelihood of extended endocrine benefit and quantifies the risk of both late (5-10 years) and overall (0-10 years) distant recurrence. BCI has recently been incorporated into the NCCN clinical practice guideline as a biomarker for prediction of benefit from extended endocrine therapy in patients with early-stage, HR+ breast cancer. The objective of the BCI Registry Study is to collect real-world evidence at a national level aimed at advancing patient care and optimizing duration of endocrine treatment and will be conducted in two phases. First, long-term patient outcomes and the impact of BCI on decision-making based on physician and patient reported outcomes as well as medication adherence to extended endocrine therapy will be assessed. Secondly, individual patient data on over 40 clinical variables will be collected and partnered with molecular profiling and genomic data for each patient to enable correlative analysis and novel biomarker research of endocrine sensitivity and resistance. Study Description: The BCI Registry Study is a prospective, multi-center, observational data registry and biospecimen repository for stage I-III HR+ breast cancer patients. The main objective of the Registry Study is prospective characterization of BCI predictive and prognostic performance. The primary endpoint is time to distant recurrence (TTDR), defined as the interval between the time of BCI testing and the first metastasis at distant organs. Secondary endpoints include time to any recurrences and medication adherence score over time. Eligibility criteria includes confirmed diagnosis of HR+ early-stage invasive breast carcinoma (ductal, lobular, or mixed ductal/lobular), either HER2 negative or positive and either node-negative or node-positive tumors with 1-3 positive lymph nodes (N1). Patients must have completed 4 to 7 years of primary adjuvant endocrine therapy and have pre-treatment tumor tissue available from a previous breast surgery or biopsy. Both physicians and patients will complete a pre- and post-test Decision Impact Questionnaire to assess the impact of BCI results on extended endocrine therapy decision-making. Patients who elect to complete 10 years of endocrine therapy will answer a Medication Adherence Questionnaire during annual follow-up visits. Follow-up of patients will end 10 years from initial breast cancer diagnosis. The Registry plans to enroll approximately 3,000 patients across approximately 40 study sites in the United States. Enrollment for the study began in Q2 2021, and 324 patients have been enrolled as of July 2021. For more information, please visit the ClinicalTrials.gov registration: NCT04875351. Citation Format: Joyce A O'Shaughnessy, Jenny R Fox, Carlos A Encarnación, Brandon O'Neal, Kai Treuner, Tara Sanft, Rachel C Jankowitz, Mark D Pegram, Catherine A Schnabel, Sami G Diab. The Breast Cancer Index registry study: A prospective multi-center observational study to evaluate patient outcome, clinical impact, and medication adherence in HR+ breast cancer patients considering treatment with extended endocrine therapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-10-01.

Breast cancer tumor heterogeneity has only little impact on the estimation of the Oncotype DX® recurrence score using Magee Equations and Magee Decision Algorithm™

Oncotype DX® assay is used to guide therapeutic decisions in early-stage invasive breast carcinoma but remains expensive. Magee Equations (MEs) and Magee Decision Algorithm(MDA) predict the Oncotype DX® recurrence score (RS) on the basis of histopathological parameters. The influence of intratumor heterogeneity on MEs and MDA remains uncertain. We compared Ki-67, estrogen and progesterone receptors, and human erb-b2 receptor tyrosine kinase 2 (HER2) status on tissue microarray cores with the corresponding findings on the whole slides to calculate MEs scores and to decide if Oncotype DX® testing was required as per MDA in two sets of 175 and 59 tumors, without and with Oncotype DX® results, respectively. Agreements in the interpretation of Ki-67, estrogen and progesterone receptors, and HER2 status were very good between limited areas and whole-slideanalyses. This resulted also in very good agreements about the results of MEs and MDA. For 7 of 175 (4%) and 3 of 59 (5.1%) cases, MEs and MDA results in different tumor areas would have changed the indication to perform or not perform Oncotype DX® assays. Oncotype DX® RSs were significantly correlated with MEs and MDA results, butamong cases initially predicted to have an RS≤25 using MDA, 3 of 34 cases (8.8%) had in fact an RS>25. Tumor heterogeneity appears to have little impact on the estimation of the Oncotype DX® RS using MEs and MDA and would have permitted to avoid half of Oncotype DX® assays in our series. Caution is nevertheless required in discarding Oncotype DX® assay in cases with ME scores >18 associated with low mitotic activity.

Tumor grade and progesterone receptor status predict 21-gene recurrence score in early stage invasive breast carcinoma.

The 21-gene recurrence score (RS) assay is increasingly utilized to predict the risk of recurrence in early stage estrogen receptor (ER)-positive breast cancer. We hypothesize that tumor grade and progesterone receptor (PR) status predict RS categorization. We identified women between the ages of 18 and 74years with stage I or II, ER-positive, invasive carcinoma of the breast from the Surveillance Epidemiology End-Results database from 2010 to 2013. Multivariable logistic regression was performed to determine factors associated with high-risk RS. We identified 42,530 patients that met inclusion criteria. Multivariable logistic regression demonstrated that grade I tumors [OR (odds ratio) 0.33, 95% CI (confidence interval) 0.31-0.37] and PR positive (PR+) status (OR 0.16, 95% CI 0.15-0.17) were significantly less likely to be associated with high-risk RS. Of patients with grade I PR+ tumors, 1% was in the high-risk group by the traditional cutoffs and 4% was in the high-risk group by the TAILORx cutoffs. The percentage of patients with high-risk RS remained low for grade I PR+ tumors regardless of age, race, tumor size, and lymph node status. We found that grade I PR+ tumors are associated a < 5% probability of having high-risk RS regardless of other patient demographic or pathologic factors. This suggests that the histologic factors of grade and PR status should be taken into consideration before ordering the 21-gene recurrence score assay.

The Effect of Receptor Status on Mastectomy and Contralateral Prophylactic Mastectomy Rates in Early Stage Invasive Breast Carcinoma

BackgroundThere is an established relationship between hormone receptor (HR; estrogen and/or progesterone receptors) status, HER2 status, and locoregional recurrence. The purpose of this study was to analyze how HR and HER2 receptor status have influenced the surgical management trends among patients with early stage breast cancer. Patients and MethodsThe National Cancer Database was queried for patients with cT1 to cT3, cN0, and cM0 breast carcinoma from 2004 to 2012. Patients were grouped on the basis of receptor status and surgical management (mastectomy or breast-conserving surgery [BCS]). Multivariable analyses were performed to investigate factors associated with increased odds of receiving mastectomy over BCS. Among a subgroup of patients who underwent ipsilateral mastectomy, analyses were performed to determine any association between contralateral prophylactic mastectomy (CPM) and receptor status. ResultsWe found 280,241 patients who met inclusion criteria for analyzing mastectomy or BCS surgical decision. Patients with HER2-positive (HER2+) tumors (HR+/HER+ and HR−/HER2+) were the most likely to undergo mastectomy (odds ratio [OR], 1.212 and 1.499 respectively, compared with HR+/HER2− patients, each P < .001). HR status alone did not affect ipsilateral surgical management as patients with HR+/HER2− and HR−/HER2− tumors demonstrated similar mastectomy rates (P = .391). Among the 108,018 who underwent mastectomy, 20% underwent CPM. After adjustment, patients with HR+/HER2+, HR−/HER2+, and HR−/HER2− were all more likely to undergo CPM (OR 1.356, 1.608, and 1.358, respectively compared with HR+/HER2− patients, each P < .001). ConclusionThis analysis indicates that patients with early stage breast cancer are more likely to undergo a mastectomy and CPM if they have HER2+ tumors.

Outcomes of Estrogen Receptor Negative and Progesterone Receptor Positive Breast Cancer

PurposeTo describe the clinical features and outcomes of estrogen receptor negative (ER-) and progesterone receptor positive (PgR+) breast cancer.MethodsWe retrospectively reviewed a well-characterized database of sequential patients diagnosed with early stage invasive breast carcinoma. Outcomes of interest were time to relapse (TTR) and overall survival (OS). Multivariable Cox proportional hazards analysis was conducted to assess the association of ER-/PgR+ with TTR and OS in comparison to ER+ and to ER- and PgR negative (ER-/PgR-) tumors irrespective of HER2 status. ER and PgR expression was conservatively defined as 10% or greater staining of cancer cells.Results815 patients were followed for a median of 40.5 months; 56 patients (7%) had ER-/PgR+, 624 (77%) had ER+ and 136 (17%) had ER-/PgR- phenotypes. Compared with ER+ tumors, ER-/PgR+ tumors were associated with younger age (50 versus 59 years, p=0.03), high grade (50% versus 24%, p<0.001) and more frequent HER2 overexpression/amplification (43% versus 14%, p<0.001). TTR for ER-/PgR+ was intermediate between ER+ and ER-/PgR- tumors, but was not significantly different from ER+ tumors. Recurrences in the ER-/PgR+ and ER-/PgR- groups occurred early in follow-up while in ER+ tumors recurrences continued to occur over the duration of follow-up. OS of ER-/PgR+ was similar to ER+ tumors and better than that of ER-/PgR- tumors.ConclusionsThe ER-/PgR+ phenotype is associated with higher grade with HER2 overexpression/amplification and occurs more commonly in younger women. Risk of relapse and death more closely resembles ER+ than ER-/PgR- tumors suggesting this phenotype represents a group of more aggressive hormone receptor positive tumors.

Clinical outcomes of estrogen receptor (ER)-negative and progesterone receptor (PgR)-positive invasive breast cancer.

567 Background: Hormone receptor (HR) expression has prognostic and predictive significance in breast cancer. Most HR-positive tumors are ER positive (ER+). In contrast, tumors that are ER negative (ER-) and PgR positive (PgR+) are uncommon and may represent an analytic artifact. We have previously shown that ER-/PgR+ tumors have been associated with younger age, higher grade, and Her2/neu over-expression suggesting a distinct biologic entity (Proceedings 103rdUSCAP Meeting). Here we evaluated clinical outcomes of ER-/PgR+ breast cancers. Methods: We retrospectively reviewed a well-characterized database comprising 816 sequential patients diagnosed with early stage invasive breast carcinoma in Salamanca, Spain. Outcomes of interest were time to relapse (TTR) and overall survival (OS). Multivariable Cox proportional hazards analysis was conducted to assess the association of ER-/PgR+ with TTR and OS in comparison to ER+ and to ER- and PgR negative (ER-/PgR-) tumors. Results: Fifty-six patients (7%) had ER-...

PO59 Breast conserving surgery and whole breast radiation therapy followed by high dose rate brachytherapy boost versus electron beam boost in the treatment of early breast cancer in young Indian women: which is cosmetically better?

Background- Breast conserving treatment (BCT) is the treatment of choice in early breast cancer. Despite years of observation it is still regarded as controversial – not in regard to the very idea; the controversy pertains rather to the way it is being performed by radiation oncologists and surgeons. There are no uniform indic-ations as far as the optimal surgery range is concerned (lumpectomy alone, lumpectomy with the macroscopic margin of 1cm, excision of the breast tissue block of a segment or a quadrant). BCT has produced survival equivalent to mastectomy in the treatment of patients with early-stage invasive breast carcinoma in several randomized Phase III clinical trials.

Breast Conservation Treatment With Radiation: An Ongoing Success Story

Breast Conservation Treatment With Radiation: An Ongoing Success Story

Outcome After Breast Conservation Treatment with Radiation for Women with Triple-Negative Early-Stage Invasive Breast Carcinoma

Background Triple-negative breast carcinoma is defined by a primary tumor that is estrogen receptor negative, progesterone receptor negative, and HER2 negative. The current study was performed to determine the relationship of triple-negative tumor status to outcome after breast conservation treatment with radiation. Patients and Methods A total of 519 women with early-stage invasive breast carcinoma underwent breast conservation treatment with radiation. Of the 519 primary breast carcinomas, 90 (17%) were triple negative and 429 (83%) were not triple negative. The median follow-up after treatment was 3.9 years. Results Compared with the patients without a triple-negative tumor, the patients with a triple-negative tumor had a higher 8-year rate of any local failure (8% vs. 4%, respectively; P = .041) and a lower 8-year rate of freedom from distant metastases (81% vs. 92%, respectively; P = .0066). There were no differences between the 2 groups for local-only first failure, overall survival, or contralateral breast cancer (all P ≥ .3). On multivariate analysis, triple-negative tumors had an increased risk for any local failure (hazard ratio, 2.58), although this difference was not statistically significant ( P = .097). Conclusion After breast conservation treatment with radiation, women with a triple-negative tumor had a higher rate of local failure compared with women without a triple-negative tumor. However, the absolute difference in local failure between the 2 groups was relatively small and therefore does not preclude breast conservation treatment with radiation for triple-negative early-stage invasive breast carcinoma.

Relationship of Breast Magnetic Resonance Imaging to Outcome After Breast-Conservation Treatment With Radiation for Women With Early-Stage Invasive Breast Carcinoma or Ductal Carcinoma in Situ

To determine the relationship of breast magnetic resonance imaging (MRI) to outcome after breast-conservation treatment (BCT) with radiation for women with early-stage invasive breast carcinoma or ductal carcinoma in situ. A total of 756 women with early stage invasive breast carcinoma or ductal carcinoma in situ underwent BCT including definitive breast irradiation during 1992 to 2001. At the time of initial diagnosis and evaluation, routine breast imaging included conventional mammography. Of the 756 women, 215 women (28%) had also undergone a breast MRI study, and 541 women (72%) had not undergone a breast MRI study. The median follow-up after treatment was 4.6 years (range, 0.1 to 13.5 years). For the women with a breast MRI study compared with the women without a breast MRI study, there were no differences in the 8-year rates of any local failure (3% v 4%, respectively; P = .51) or local-only first failure (3% v 4%, respectively; P = .32). There were also no differences between the two groups for the 8-year rates of overall survival (86% v 87%, respectively; P = .51), cause-specific survival (94% v 95%, respectively; P = .63), freedom from distant metastases (89% v 92%, respectively; P = .16), or contralateral breast cancer (6% v 6%, respectively; P = .39). The use of a breast MRI study at the time of initial diagnosis and evaluation was not associated with an improvement in outcome after BCT with radiation.

Predicting the extent of invasive disease by MRI to enhance the use of minimally invasive techniques in the management of early stage breast carcinoma

610 Background: With the advent of minimally invasive procedures such as radio-frequency ablation and vacuum-assisted core biopsy for managing early-stage invasive breast carcinoma, the ability to predict invasive disease by pre-procedure imaging is essential to achieving an adequate margin and for guiding adjuvant therapy. Magnetic resonance imaging (MRI) is a sensitive modality used in the detection of breast pathology and may provide the anatomic resolution necessary to predict the extent of invasive disease. Methods: A retrospective review was conducted on MRI and pathologic data from 24 (63%) of 38 patients with focal, invasive breast carcinoma enrolled in an ongoing multi-modality imaging study between 3/02 and 10/03. Patients were selected on the basis of the following criteria: 1) 1 or 2 suspicious focal lesions per breast detected on MRI, 2) 1 or 2 pathologically-proven foci of invasive carcinoma per breast, and 3) no chemotherapy between MRI and definitive surgery. Largest tumor dimension as measured by MRI, performed prior to definitive surgery, was compared to the largest pathologic tumor dimension. Results: Median age of selected patients was 52.0 y (range 37.9–71.1). 25 lesions were evaluated. Histology revealed 20 (80%) invasive ductal carcinomas, 3 (12%) invasive lobular carcinomas, and 2 (8%) mixed lesions. Seven patients underwent reexcision due to positive margins with no further invasive carcinoma identified. Median lesion size by MRI was 2.0 cm (0.7–3.4). Median lesion size by pathology was 1.9 cm (0.8–4.0). For lesions ≤ 2 cm by pathology (n =16), MRI size was equal to or greater than pathologic size for 14 lesions (88%) and the difference between MRI and pathologic size was within 0.5 cm in 12 lesions (75%). Conclusion: MRI was effective at estimating invasive breast carcinoma dimension in lesions less than 2 cm. MRI avoided underestimation of pathologic size in small lesions, making it a potentially safe means of identifying the target for minimally invasive techniques. No significant financial relationships to disclose.

Surgical treatment of early-stage breast cancer in the department of defense healthcare system

BACKGROUND: The choice between breast-conserving surgery and modified radical mastectomy in the treatment of women with early stage breast cancer in the Department of Defense Healthcare System may be influenced by demographic factors. STUDY DESIGN: The Department of Defense Automated Central Tumor Registry (ACTUR) was queried for women diagnosed with American Joint Committee on Cancer Stage I or II invasive breast carcinoma from January 1, 1986, to December 31, 1996. Univariate analysis and multivariate analysis were applied to the study variables. Year of diagnosis, age at diagnosis, tumor size, type of hospital, geographic region, and local availability of radiation therapy were evaluated with respect to the type of surgical treatment performed. Surgical treatment was either breast conservation therapy (BCT) or modified radical mastectomy. RESULTS: After excluding women for whom the data were incomplete (n = 308), 7,815 women were identified who met study criteria. There was a progressive increase in the use of BCT to treat tumors of all sizes from 16% to 47% over the 11 years of the study (p < 0.0001). BCT was more frequently used for smaller tumors (< 2 cm), with an odds ratio of 2.46 (2.20–2.76, 95% CI). In 1996, 54% of women with T1 (< 2 cm) tumors were treated with BCT. Women treated with BCT were nearly the same age as those undergoing modified radical mastectomy (55.5 years versus 56.8 years, p < 0.0001). BCT was used at a slightly greater rate in medical centers than in community hospitals (31% versus 28%, p < 0.0001). Use of BCT varied among geographic regions from a low of 24% in the southwestern USA to a peak of 36% in the Northeast and 40% in hospitals outside of the continental United States (p < 0.0001). Local availability of radiation therapy did not influence choice of treatment. CONCLUSIONS: The use of BCT to treat early stage invasive breast carcinoma in the Department of Defense Healthcare System is increasing. But BCT is used less often to treat larger tumors. Regional differences in the use of BCT persist, even after controlling for other factors. Patient age and type of hospital (community versus academic center) appear to exert little influence on the choice of treatment. Local availability of radiation therapy did not seem to influence the choice of treatment. Our data suggest that efforts to promote the use of BCT should target the central and southwestern USA. Use of BCT should also be emphasized for women with larger tumors (> 2 cm).

Breast conservation therapy in the United States following the 1990 National Institutes of Health Consensus Development Conference on the treatment of patients with early stage invasive breast carcinoma

A National Institutes of Health (NIH) Consensus Development Conference on the treatment of patients with early stage invasive breast carcinoma, held in June 1990, recommended breast conservation therapy for the majority of women with Stage I or II breast carcinoma. The authors evaluated the national use of breast conservation therapy before and after the conference to determine whether the conference had had an impact on utilization. Women with Stage I or II breast carcinoma (n = 109,880), diagnosed during the years 1983-1995, were identified via 9 population-based cancer registries of the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. The likelihood of breast conservation surgery versus mastectomy and, among women who underwent breast conservation surgery, the likelihood of postoperative radiation therapy versus none, were assessed for 3 time periods (January 1983 to April 1985, May 1985 to June 1990, and July 1990 to December 1995). Associations between the use of breast conservation surgery or postoperative radiotherapy according to patient stage, age, race, and region were compared among women diagnosed before and after the NIH Consensus Development Conference. From 1985 (the year that the U.S. randomized controlled trial demonstrating equivalent efficacy between breast conservation therapy and mastectomy was published) through 1989, approximately 35% of women with Stage I and 19% of women with Stage II breast carcinoma underwent breast conservation surgery; these percentages remained constant throughout this period. Beginning in 1990, the year of the NIH Consensus Development Conference, the use of breast conservation surgery increased in each subsequent year; by 1995, 60% of women with Stage I and 39% of women with Stage II breast carcinoma received such treatment. However, regional variation in use was observed (Stage I, range 41.4-71.4% for 1995) and no registry reported breast conservation therapy for the majority of women with Stage II disease (range, 23.8-48.0%). The use of postoperative radiotherapy for women who underwent breast conservation surgery was similar in the periods before and after the conference. Although breast conservation therapy was performed more frequently following the NIH Consensus Development Conference, variation in use by region of the U.S. suggests the continued presence of barriers to widespread adoption of the recommendations formulated at the conference.

Breast conservation therapy in the United States following the 1990 National Institutes of Health Consensus Development Conference on the treatment of patients with early stage invasive breast carcinoma

BACKGROUND A National Institutes of Health (NIH) Consensus Development Conference on the treatment of patients with early stage invasive breast carcinoma, held in June 1990, recommended breast conservation therapy for the majority of women with Stage I or II breast carcinoma. The authors evaluated the national use of breast conservation therapy before and after the conference to determine whether the conference had had an impact on utilization. METHODS Women with Stage I or II breast carcinoma (n = 109,880), diagnosed during the years 1983–1995, were identified via 9 population-based cancer registries of the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. The likelihood of breast conservation surgery versus mastectomy and, among women who underwent breast conservation surgery, the likelihood of postoperative radiation therapy versus none, were assessed for 3 time periods (January 1983 to April 1985, May 1985 to June 1990, and July 1990 to December 1995). Associations between the use of breast conservation surgery or postoperative radiotherapy according to patient stage, age, race, and region were compared among women diagnosed before and after the NIH Consensus Development Conference. RESULTS From 1985 (the year that the U.S. randomized controlled trial demonstrating equivalent efficacy between breast conservation therapy and mastectomy was published) through 1989, approximately 35% of women with Stage I and 19% of women with Stage II breast carcinoma underwent breast conservation surgery; these percentages remained constant throughout this period. Beginning in 1990, the year of the NIH Consensus Development Conference, the use of breast conservation surgery increased in each subsequent year; by 1995, 60% of women with Stage I and 39% of women with Stage II breast carcinoma received such treatment. However, regional variation in use was observed (Stage I, range 41.4–71.4% for 1995) and no registry reported breast conservation therapy for the majority of women with Stage II disease (range, 23.8–48.0%). The use of postoperative radiotherapy for women who underwent breast conservation surgery was similar in the periods before and after the conference. CONCLUSIONS Although breast conservation therapy was performed more frequently following the NIH Consensus Development Conference, variation in use by region of the U.S. suggests the continued presence of barriers to widespread adoption of the recommendations formulated at the conference. Cancer 1999;86:628–37. © 1999 American Cancer Society.

Prognosis following local or regional recurrence after conservative surgery and radiotherapy for early stage breast carcinoma

Factors which influence patient prognosis following a breast recurrence or regional nodal recurrence after initial treatment of early-stage invasive breast carcinoma with conservative surgery and radiotherapy are not well known. Ninety patients treated at the Joint Center for Radiation Therapy treated from 1968–1981 had a recurrence in the treated breast before (84) or simultaneous with (6) distant metastases. Sixty-five patients had salvage mastectomy (median subsequent follow-up in patients without further disease, 32 months; range, 1–123 months). The five-year rate of further recurrence in this group was 37%. The most important variable associated with subsequent outcome was the histology of the recurrent tumor. There were no further recurrences among 10 patients with purely noninvasive cancer or 10 patients with predominantly non-invasive disease and only focal areas of invasion. In contrast, 17 45 patients (38%) with predominantly infiltrating tumors suffered further local-regional recurrences (6) or distant metastases (11) following mastectomy (5-year actuarial rate, 55%) ( p < 0.05). Ten patients developed regional nodal failures without evidence of simultaneous breast recurrence (1 internal mammary, 3 supraclavicular, 1 both supraclavicular and axillary, and 5 axillary). Only 3 of these 10 (all with axillary node failures) did not have simultaneous distant metastases; they remain alive without evidence of further distant or local-regional recurrence following salvage treatment 1, 59, and 87 months after recurrence. We conclude that the great majority of the patients (88% in this series) who have a breast recurrence following initial conservative surgery and radiation therapy for early stage breast carcinoma will have disease limited to the breast clinically and tumors amenable to salvage mastectomy. Salvage mastectomy appears to be effective treatment for patients with an isolated breast recurrence, especially if the recurrence is predominantly or wholly non-invasive.