Overdiagnosis and Overtreatment of Breast Cancer

Author(s):  
Michael Alvarado ◽  
Elissa Ozanne ◽  
Laura Esserman

Overview: Breast cancer is the most common cancer in women. Through greater awareness, mammographic screening, and aggressive biopsy of calcifications, the proportion of low-grade, early stage cancers and in situ lesions among all breast cancers has risen substantially. The introduction of molecular testing has increased the recognition of lower risk subtypes, and less aggressive treatments are more commonly recommended for these subtypes. Mammographically detected breast cancers are much more likely to have low-risk biology than symptomatic tumors found between screenings (interval cancers) or that present as clinical masses. Recognizing the lower risk associated with these lesions and the ability to confirm the risk with molecular tests should safely enable the use of less aggressive treatments. Importantly, ductal carcinoma in situ (DCIS) lesions, or what have been called stage I cancers, in and of themselves are not life-threatening. In situ lesions have been treated in a manner similar to that of invasive cancer, but there is little evidence to support that this practice has improved mortality. It is also being recognized that DCIS lesions are heterogeneous, and a substantial proportion of them may in fact be precursors of more indolent invasive cancers. Increasing evidence suggests that these lesions are being overtreated. The introduction of molecular tests should be able to help usher in a change in approach to these lesions. Reclassifying these lesions as part of the spectrum of high-risk lesions enables the use of a prevention approach. Learning from the experience with active surveillance in prostate cancer should empower the introduction of new approaches, with a focus on preventing invasive cancer, especially given that there are effective, United States Food and Drug Administration (FDA)-approved breast cancer preventive interventions.

2018 ◽  
Vol 36 (20) ◽  
pp. 2070-2077 ◽  
Author(s):  
Janie M. Lee ◽  
Linn Abraham ◽  
Diana L. Lam ◽  
Diana S.M. Buist ◽  
Karla Kerlikowske ◽  
...  

Purpose The aim of the current study was to characterize the risk of interval invasive second breast cancers within 5 years of primary breast cancer treatment. Methods We examined 65,084 surveillance mammograms from 18,366 women with a primary breast cancer diagnosis of unilateral ductal carcinoma in situ or stage I to III invasive breast carcinoma performed from 1996 to 2012 in the Breast Cancer Surveillance Consortium. Interval invasive breast cancer was defined as ipsilateral or contralateral cancer diagnosed within 1 year after a negative surveillance mammogram. Discrete-time survival models—adjusted for all covariates—were used to estimate the probability of interval invasive cancer, given the risk factors for each surveillance round, and aggregated across rounds to estimate the 5-year cumulative probability of interval invasive cancer. Results We observed 474 surveillance-detected cancers—334 invasive and 140 ductal carcinoma in situ—and 186 interval invasive cancers which yielded a cancer detection rate of 7.3 per 1,000 examinations (95% CI, 6.6 to 8.0) and an interval invasive cancer rate of 2.9 per 1,000 examinations (95% CI, 2.5 to 3.3). Median cumulative 5-year interval cancer risk was 1.4% (interquartile range, 0.8% to 2.3%; 10th to 90th percentile range, 0.5% to 3.7%), and 15% of women had ≥ 3% 5-year interval invasive cancer risk. Cumulative 5-year interval cancer risk was highest for women with estrogen receptor– and progesterone receptor–negative primary breast cancer (2.6%; 95% CI, 1.7% to 3.5%), interval cancer presentation at primary diagnosis (2.2%; 95% CI, 1.5% to 2.9%), and breast conservation without radiation (1.8%; 95% CI, 1.1% to 2.4%). Conclusion Risk of interval invasive second breast cancer varies across women and is influenced by characteristics that can be measured at initial diagnosis, treatment, and imaging. Risk prediction models that evaluate the risk of cancers not detected by surveillance mammography should be developed to inform discussions of tailored surveillance.


Author(s):  
Julia White

Breast radiotherapy after lumpectomy is considered standard for nearly all patients with invasive breast cancer and is recommended for many patients after lumpectomy for ductal carcinoma in situ (DCIS). However, there is recognition that lumpectomy alone can achieve optimal cancer control for some patients with invasive breast cancer and DCIS. Patients with breast cancers with lower risk of recurrence are less likely to derive benefit from breast radiotherapy. This review will focus on defining populations of patients with invasive breast cancer and DCIS with a low risk of recurrence post-lumpectomy and the evidence supporting omission of breast radiotherapy post-lumpectomy.


1999 ◽  
Vol 435 (4) ◽  
pp. 413-421 ◽  
Author(s):  
Tetsunari Oyama ◽  
Horacio Maluf ◽  
F. Koerner

Breast Care ◽  
2019 ◽  
Vol 15 (4) ◽  
pp. 386-391
Author(s):  
Benedict Krischer ◽  
Serafino Forte ◽  
Gad Singer ◽  
Rahel A. Kubik-Huch ◽  
Cornelia Leo

Purpose: The question of overtreatment of ductal carcinoma in situ (DCIS) was raised because a significant proportion of especially low-grade DCIS lesions never progress to invasive cancer. The rationale for the present study was to analyze the value of stereotactic vacuum-assisted biopsy (VAB) for complete removal of DCIS, focusing on the relationship between the absence of residual microcalcifications after stereotactic VAB and the histopathological diagnosis of the definitive surgical specimen. Patients and Methods: Data of 58 consecutive patients diagnosed with DCIS by stereotactic VAB in a single breast center between 2012 and 2017 were analyzed. Patient records from the hospital information system were retrieved, and mammogram reports and images as well as histopathology reports were evaluated. The extent of microcalcifications before and after biopsy as well as the occurrence of DCIS in biopsy and definitive surgical specimens were analyzed and correlated. Results: There was no correlation between the absence of residual microcalcifications in the post-biopsy mammogram and the absence of residual DCIS in the final surgical specimen (p = 0.085). Upstaging to invasive cancer was recorded in 4 cases (13%) but occurred only in the group that had high-grade DCIS on biopsy. Low-grade DCIS was never upgraded to high-grade DCIS in the definitive specimen. Conclusions: The radiological absence of microcalcifications after stereotactic biopsy does not rule out residual DCIS in the final surgical specimen. Since upstaging to invasive cancer is seen in a substantial proportion of high-grade DCIS, the surgical excision of high-grade DCIS should remain the treatment of choice.


2014 ◽  
Vol 80 (10) ◽  
pp. 944-947
Author(s):  
Victoria O'connor ◽  
Elizabeth Arena ◽  
Joslyn Albright ◽  
Nefertiti Brown ◽  
Ryan O'connor ◽  
...  

Radiologic–pathologic correlation of lesions diagnosed by magnetic resonance (MR) is precluded by insufficient data on histological characteristics of lesions suspicious on MR but not visible on concurrent mammogram or ultrasound. The objective of this study was to describe histological features of breast lesions diagnosed exclusively by MR. The participants underwent MR-guided breast biopsy between 2007 and 2012 for a suspicious lesion not identified by mammography or ultrasound. Histology slides were interpreted retrospectively by a breast pathologist. Of 126 patients (126 lesions), 34 (27%) had new breast cancer, 51 (40.5%) previous breast cancer, and 41 (32.5%) dense breasts or a significant family history of breast cancer. MR identified 23 (18.3%) invasive cancers: 20 were Grade 1 and 17 were ductal. Of the 126 lesions, 16 (13%) were ductal carcinoma in situ (DCIS), four were atypical ductal hyperplasia and atypical lobular hyperplasia (3%), and 68 (54%) were benign. Fifteen biopsies (12%) had no significant pathology. Five DCIS lesions were upgraded to T1 invasive cancers. Approximately 30 per cent of suspicious lesions detected exclusively by MR are invasive or in situ cancers that are predominantly low grade. Further studies are needed to determine if malignant lesions can be prospectively distinguished by MR characteristics.


ISRN Oncology ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Andrei Dobrescu ◽  
Monique Chang ◽  
Vatsala Kirtani ◽  
George K. Turi ◽  
Randa Hennawy ◽  
...  

Background. To our knowledge, the hormone receptor status of noncontiguous ductal carcinoma in situ (DCIS) occurring concurrently in ER/PgR-negative invasive cancer has not been studied. The current study was undertaken to investigate the ER/PgR receptor status of DCIS of the breast in patients with ER/PgR-negative invasive breast cancer. Methods. We reviewed the immunohistochemical (IHC) staining for ER and PgR of 187 consecutive cases of ER/PgR-negative invasive breast cancers, collected from 1995 to 2002. To meet the criteria for the study, we evaluated ER/PgR expression of DCIS cancer outside of the invasive breast cancer. Results. A total of 37 cases of DCIS meeting the above criteria were identified. Of these, 16 cases (43.2%) showed positive staining for ER, PgR, or both. Conclusions. In our study of ER/PgR-negative invasive breast cancer we found that in 8% of cases noncontiguous ER/PR-positive DCIS was present. In light of this finding, it may be important for pathologists to evaluate the ER/PgR status of DCIS occurring in the presence of ER/PgR-negative invasive cancer, as this subgroup could be considered for chemoprevention.


Breast Care ◽  
2020 ◽  
Vol 15 (4) ◽  
pp. 355-365
Author(s):  
Julian Puppe ◽  
Tabea Seifert ◽  
Christian Eichler ◽  
Henryk Pilch ◽  
Peter Mallmann ◽  
...  

Background: Breast cancer is a very heterogeneous disease and luminal breast carcinomas represent the hormone receptor-positive tumors among all breast cancer subtypes. In this context, multigene signatures were developed to gain further prognostic and predictive information beyond clinical parameters and traditional immunohistochemical markers. Summary: For early breast cancer patients these molecular tools can guide clinicians to decide on the extension of endocrine therapy to avoid over- and undertreatment by adjuvant chemotherapy. Beside the predictive and prognostic value, a few genomic tests are also able to provide intrinsic subtype classification. In this review, we compare the most frequently used and commercially available molecular tests (OncotypeDX®, MammaPrint®, Prosigna®, EndoPredict®, and Breast Cancer IndexSM). Moreover, we discuss the clinical utility of molecular profiling for advanced breast cancer of the luminal subtype. Key Messages: Multigene assays can help to de-escalate systemic therapy in early-stage breast cancer. Only the Oncotype DX® and MammaPrint®test are validated by entirely prospective and randomized phase 3 trials. More clinical evidence is needed to support the use of genomic tests in node-positive disease. Recent developments in high-throughput sequencing technology will provide further insights to understand the heterogeneity of luminal breast cancers in early-stage and metastatic disease.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11630-e11630
Author(s):  
N. Gercovich ◽  
E. Gil Deza ◽  
M. Russo ◽  
C. Garcia Gerardi ◽  
C. Diaz ◽  
...  

e11630 Introduction: Male breast cancer is very rare, representing only between 0.7% and 1% of all breast cancers, and only half of them are early stage cases. Objective: The present study has been designed with the aim of studying retrospectively the clinical onset and evolution of male invasive breast cancer patients (stages I and II) treated at IOHM between 1997 and 2008. Methods: The records of 3,000 breast cancer cases followed between 1997 and 2008 were searched, looking for male stage I and II breast cancer patients. A database was designed following the recommendations of the Directors of Surgical Pathology of the USA. The information registered encompassed: adjuvant treatments, recurrence date and date of final consultation or death. Results: Twelve pts were identified. Mean age (range)= 66 yo (50–89 yo). Tumoral type= Invasive Ductal Carcinoma 12 pt. Tumoral subtype= NOS 9 pt (75%) Apocrine 2 pt (17%) Micropapillar 1 pt (8%). Nottingham´s grade= Grade 2: 8 pt, Grade 3: 3 pt, N/A=1 pt. Stage= I= 6 pt, II=6 pt. ER (Positve= 9 pt, Negative=1 pt, N/A= 2 pt). PR (Positve= 8 pt, Negative= 2 pt, N/A=2 pt). Her2neu (0+= 3 pt, 1+= 3 pt, 2+= 2 pt, N/A= 4 pt). Surgery= Mastectomy= 11 pt, Lumpectomy 1= pt. Radiotherapy=5 pt. Adjuvance= No=2 pt, Hormonotherapy (HT)= 3 pt, Chemotherapy (CHT) = 3 pt, CHT+HT= 4 pt. Recurrence= Yes= 2 pt, No= 10 pt. Survival: Dead= 1 pt, Alive =11 pt. Mean Time To Progression= Stage I =66 months, Stage II =42 months. Global survival: Stage I =66 months, Stage II =52 months. Conclusions: 1. Twelve stage I and II male breast cancer patients were identified out of 3000 (0.4%) breast cancer cases diagnosed and followed in the past 10 years at the IOHM. 2. Mastectomy was the surgical procedure in 11 of the 12 cases 3. Ten pt underwent adjuvant treatment. 4. With a mean follow up time of 60 months, all stage I patients are alive and there were no recurrences. Two of the 6 stage II pts progressed and one died. No significant financial relationships to disclose.


2021 ◽  
Author(s):  
Siri H Strand ◽  
Belen Rivero-Gutierrez ◽  
Kathleen E Houlahan ◽  
Jose A Seoane ◽  
Lorraine King ◽  
...  

Ductal carcinoma in situ (DCIS) is the most common precursor of invasive breast cancer (IBC), with variable propensity for progression. We have performed the first multiscale, integrated profiling of DCIS with clinical outcomes by analyzing 677 DCIS samples from 481 patients with 7.1 years median follow-up from the Translational Breast Cancer Research Consortium (TBCRC) 038 study and the Resource of Archival Breast Tissue (RAHBT) cohorts. We made observations on DNA, RNA, and protein expression, and generated a de novo clustering scheme for DCIS that represents a fundamental transcriptomic organization at this early stage of breast neoplasia. Distinct stromal expression patterns and immune cell compositions were identified. We found RNA expression patterns that correlate with later events. Our multiscale approach employed in situ methods to generate a spatially resolved atlas of breast precancers, where complementary modalities can be directly compared and correlated with conventional pathology findings, disease states, and clinical outcome.


2021 ◽  
Author(s):  
Daniela Nachmanson ◽  
Adam Officer ◽  
Hidetoshi Mori ◽  
Jonathan Gordon ◽  
Mark F. Evans ◽  
...  

The increased detection and treatment of early stage breast cancer as well as ductal carcinoma in situ (DCIS) has not led to significant survival benefits. Therefore, the current standard treatment of DCIS is questionable. An informed evidence-based treatment strategy, and likely de-escalation from the current standards requires new prognostic models built from more comprehensive characterization with objective criteria. Parallel profiling of the molecular landscape and micro-environment in pure DCIS remains challenging due to histological heterogeneity and the inevitable reliance on small archived specimens. Leveraging recent methodological advances, we characterized the mutational, transcriptional, histological and microenvironmental landscape across multiple micro-dissected regions from 39 cases to generate a multi-modal breast precancer atlas. The histological architecture was associated with grade, adiposity, and intrinsic expression subtypes. Similar to previous findings, high-grade lesions had higher mutational burden, including TP53 mutations, while low-grade lesions had more frequent 16q losses and GATA3 mutations. Multi-region analysis revealed most somatic alterations, including whole genome duplication events, were clonal, but genetic divergence increased with distance between regions. In 7/12 evaluable cases, somatic mutations in putative driver genes affected a subset of regions only. This genetic heterogeneity often accompanied phenotypic heterogeneity and regions with low risk features (Normal-like, Luminal A) occurred earlier than those with high-risk features (Her2-like, Basal or necrosis) according to the phylogenetic analysis. The immune-environment was evaluated using multiplex immuno-histochemistry to measure relative stromal and epithelial densities of B lymphocyte (B-cell), T lymphocyte (T-cell) and regulatory T cells (T-reg) and identify 3 immune-states: Active, Suppressed and Excluded (lower epithelial density). All states included both DCIS and adjacent benign regions, and none associated with intrinsic subtypes. The Excluded state was enriched in high-grade DCIS and, compared to benign areas, more likely acquired in DCIS, showing transcriptional evidence of stronger immune-suppression and possible evasion. The breast pre-cancer atlas therefore reveals correlated levels of phenotypic and genotypic heterogeneity, including at sub-histological resolution. These uniquely integrated observations will help scope future studies, prioritize candidate markers for progression risk modelling and identify functional similarities in precursor lesions from other types of adenocarcinomas.


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