Long-term prognosis is associated with residual disease after neoadjuvant systemic therapy but not with initial nodal status

Key Points Patients with Hurler syndrome show significant residual disease burden despite HCT. Early referral for HCT, using noncarrier donors and regimens designed to achieve full-donor chimerism, offers the best long-term prognosis.

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To Look or Not to Look? Yes to Nodal US!

Journal of Breast Imaging ◽

10.1093/jbi/wbab079 ◽

2021 ◽

Author(s):

Gaiane M Rauch ◽

Henry M Kuerer ◽

Maxine S Jochelson

Keyword(s):

Breast Cancer ◽

Systemic Therapy ◽

Tumor Biology ◽

Significant Proportion ◽

Nodal Status ◽

Newly Diagnosed ◽

Breast Cancer Patients ◽

Axillary Surgery ◽

Appropriate Treatment ◽

Neoadjuvant Systemic Therapy

Abstract Knowledge of axillary nodal status is highly important for correct staging and treatment planning in patients with breast cancer. Axillary US is a recognized highly specific and cost-effective tool for assessing nodal status and guiding appropriate treatment. Axillary US imaging with US-guided biopsy is routinely performed throughout the world. However, because of recent developments in the surgical management of the axilla in patients with newly diagnosed breast cancer (American College of Surgeons Oncology Group [ACOSOG] Z0011 trial) and in patients with breast cancer receiving neoadjuvant systemic therapy (ACOSOG Z1071, SENTinel NeoAdjuvant [SENTINA] and Sentinel Node biopsy aFter NeoAdjuvant Chemotherapy [SN FNAC] trials), some have questioned the utility of axillary US for nodal staging. Here, we review the evidence to date supporting the additional value of axillary US for patients with breast cancer. Nodal US in patients with newly diagnosed breast cancer is useful for staging; in a significant proportion of patients, nodal US identifies additional axillary level II or level III nodal disease, which allows for appropriate treatment of disease. Furthermore, ongoing clinical trials may show that axillary surgery can be omitted in patients with negative findings on axillary US. In patients with lymph node–positive disease undergoing neoadjuvant systemic therapy, nodal US can guide the approach to axillary surgery. A more personalized patient approach, taking into the account tumor biology, among other factors, may help to mitigate the controversy surrounding the role of axillary US in breast cancer patients.

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The persistence of disseminated tumor cells after systemic therapy and their influence on prognosis in early breast cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.1030 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 1030-1030

Author(s):

Andreas D. Hartkopf ◽

Markus Wallwiener ◽

Ines Gruber ◽

Hans Neubauer ◽

Markus Hahn ◽

...

Keyword(s):

Breast Cancer ◽

Multivariate Analysis ◽

Endocrine Therapy ◽

Tumor Cells ◽

Early Breast Cancer ◽

Systemic Therapy ◽

Disseminated Tumor Cells ◽

Nodal Status ◽

Neoadjuvant Systemic Therapy ◽

The Impact

1030 Background: Detection of disseminated tumor cells (DTC) in the bone marrow (BM) of early breast cancer (EBC) patients before the administration of systemic therapy is associated with poor outcome. The aim of this study was to evaluate the impact of DTC on overall survival (OS) and disease free survival (DFS) in a large cohort of EBC patients after the administration of systemic therapy. Methods: EBC patients receiving systemic therapy (endocrine therapy and/or chemotherapy +/- HER2-directed treatment) either prior to surgery (neoadjuvant systemic therapy, NST) or after surgery (adjuvant systemic therapy, AST) at Tuebingen University Hospital, Germany between 01/2003 and 06/2012 were available for this analysis. BM aspirates were collected during surgery / one year after surgery in patients receiving NST / AST. DTC were identified by immunocytochemistry (pancytokeratin antibody A45/B3) and cytomorphology. Survival was analyzed using univariate (log-rank test) and multivariate analysis (cox regression). Results: DTC were detected in 201 of 608 (35%) patients. 175 of 419 (42%) patients treated with NST and 35 of 189 (19%) patients treated with AST were DTC-positive. Chemotherapy / endocrine therapy was administered prior to BM aspiration in 399 (96%) / 19 (5%) of the patients receiving NST and in 99 (52%) / 158 (84%) of the patients receiving AST. On univariate analysis, the detection of DTC was a significant predictor of poor DFS (HR: 2.27, 95% CI: 1.48 – 3.48, p<0.001) and poor OS (HR: 1.89, 95% CI: 1.19 – 3.00, p=0.007). On multivariate analysis (considering all clinicopathological factors and the DTC-status), independent factors for DFS were DTC-status (negative vs. positive), grading (G2-3 vs. G3), nodal-status (negative vs. positive), and the ER-status (negative vs. positive). Independent factors for OS were grading, PR-status (negative vs. positive) and nodal-status. Conclusions: The persistence of DTC in the BM of EBC patients after systemic treatment is a strong and independent marker of poor prognosis. Determination of the DTC-status is thus promising to monitor the effect of systemic therapy and to identify patients that are in need of additional adjuvant therapy.

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De-Escalating Axillary Surgery in Node-Positive Breast Cancer Treated with Neoadjuvant Systemic Therapy

Breast Care ◽

10.1159/000518376 ◽

2021 ◽

pp. 1-6

Author(s):

Sabine R. de Wild ◽

Janine M. Simons ◽

Marie-Jeanne T.F.D. Vrancken Peeters ◽

Marjolein L. Smidt ◽

Linetta B. Koppert

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Systemic Therapy ◽

Axillary Staging ◽

Breast Cancer Patients ◽

Less Invasive ◽

Node Positive ◽

Neoadjuvant Systemic Therapy ◽

Positive Breast Cancer

Background: There is a trend towards de-escalating axillary staging and treatment in breast cancer patients. On account of neoadjuvant systemic therapy, node-positive breast cancer patients can achieve a pathological complete response of the axilla. It is hypothesized that these patients do not benefit from an axillary lymph node dissection (ALND), and thus may be spared the risk of severe post-surgical morbidity. In an effort to omit standard ALND, less invasive axillary staging procedures are being implemented to establish response-guided treatment. However, it is unclear which less invasive staging procedure is most accurate, and long-term data are missing with regard to their oncologic safety. Summary: This article provides an overview of the literature on currently used less invasive axillary staging procedures, the accuracy and feasibility of these procedures in clinical practice, important issues concerning axillary treatment, and issues to be addressed in ongoing or future studies. Key messages: More evidence is needed regarding the safety of replacing standard ALND by less invasive axillary staging procedures in terms of long-term prognosis. These less invasive staging procedures not only serve to select patients who may benefit from treatment de-escalation, but also to select patients who may benefit from treatment escalation.

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Abstract P5-08-07: The long-term prognosis of breast cancers patients diagnosed ≤40 years in the absence of adjuvant systemic therapy

10.1158/1538-7445.sabcs16-p5-08-07 ◽

2017 ◽

Author(s):

GMHE Dackus ◽

ND Ter Hoeve ◽

M Opdam ◽

W Vreuls ◽

EA Koop ◽

...

Keyword(s):

Systemic Therapy ◽

Adjuvant Systemic Therapy ◽

Breast Cancers ◽

Long Term Prognosis

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Reappraisal of the role of axillary lymph node dissection in the conservative treatment of breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1997.15.2.691 ◽

1997 ◽

Vol 15 (2) ◽

pp. 691-700 ◽

Cited By ~ 69

Author(s):

B G Haffty ◽

B Ward ◽

P Pathare ◽

R Salem ◽

C McKhann ◽

...

Keyword(s):

Lymph Node ◽

Lymph Node Dissection ◽

Systemic Therapy ◽

Axillary Lymph Node ◽

Nodal Status ◽

Axillary Lymph ◽

Node Dissection ◽

Term Outcome ◽

Long Term Outcome

PURPOSE The purpose of this study was (1) to review systemic therapy practice patterns to assess how information regarding nodal status currently influences systemic therapy decisions, and (2) to review long-term outcome of patients who do not undergo axillary dissection compared with patients who do. METHODS AND MATERIALS For the current practice patterns portion of the study, the records of 292 patients who presented in the past 3 years with invasive breast cancer and underwent conservative surgery were reviewed to determine systemic therapy administered with respect to patient age, primary tumor size, clinical nodal status, and presenting symptoms. For the long-term outcome portion of the study, the records of 955 patients with invasive breast cancer who underwent conservative surgery and radiation therapy before December 1989 were reviewed. Patient characteristics and outcome of those patients who underwent axillary dissection (n = 565, 59%) were compared with a cohort of patients treated during the same era who did not undergo axillary dissection (n = 390, 41%). RESULTS For the current practice-patterns cohort, information regarding nodal status appeared to influence adjuvant systemic therapy for those patients less than 50 years of age and for those patients with palpable masses who were older than 50. Patients older than 50 with nonpalpable mammographically detected tumors have a low probability of nodal involvement and information regarding nodal status rarely changed therapy in this group of patients. In the long-term outcome study, there were no significant differences in the rates of distant metastasis, disease-free survival, or overall survival between those patients who underwent lymph node dissection and those who did not. CONCLUSION For selected patients, axillary lymph node dissection appears to have little influence on subsequent management and long-term outcome. These data suggest that it is time to reassess the role of axillary lymph node dissection in patients who undergo conservative surgery and radiation therapy.

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Best Foot Forward: Neoadjuvant Systemic Therapy as Standard of Care in Triple-Negative and HER2-Positive Breast Cancer

American Society of Clinical Oncology Educational Book ◽

10.1200/edbk_281381 ◽

2020 ◽

pp. e1-e16

Author(s):

Priyanka Sharma ◽

Roisin M. Connolly ◽

Evanthia T. Roussos Torres ◽

Alastair Thompson

Keyword(s):

Breast Cancer ◽

Systemic Therapy ◽

Residual Disease ◽

Early Stage ◽

Treatment Strategies ◽

Long Term Outcomes ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

Neoadjuvant systemic treatment of early-stage breast cancer has been used to improve resectability and reduce the extent of breast and axillary surgery. More recently, several other merits of neoadjuvant systemic treatment have emerged, including the ability to tailor clinically available adjuvant systemic therapy options based on pathologic response and to serve as a platform for early assessment of novel agents and response biomarkers and as an avenue for treatment optimization investigations (local and systemic therapy escalation and de-escalation trials guided by pathologic response). Attainment of a pathologic complete response (pCR) is associated with excellent long-term outcomes; conversely, the presence of residual disease is associated with a high risk of recurrence for patients with HER2-positive breast cancer and triple-negative breast cancer (TNBC). Treatment strategies in early-stage HER2-positive breast cancer include regimens incorporating trastuzumab, pertuzumab, ado-trastuzumab emtansine, and neratinib, resulting in high pCR rates and overall excellent long-term outcomes. Currently available cytotoxic regimens yield pCR for 35% to 55% of patients with TNBC, and immune checkpoint inhibition is showing early promise for this subtype. New drug and predictive biomarker evaluations in the neoadjuvant setting aim to develop optimal treatment strategies for the individual patient, with the ultimate goal of maximizing efficacy and minimizing toxicity. Research efforts involving novel agents are being undertaken to address the high risk of recurrence for patients with residual disease. Omission of breast surgery following neoadjuvant chemotherapy requires further development of imaging and biopsy techniques to accurately assess the extent of residual disease before clinical application.

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