Adjuvant Therapy in Breast Cancer Patients With Microscopic Residual Disease.

INTRODUCTION: Surgical resection is the gold standard for early-stage breast cancer. Positive surgical margins are associated with poor outcome. Endocrine therapy (ET) is recommended as primary systemic treatment for hormone receptor positive (HR+) breast cancer after surgery. We hypothesized that chemoenocrine therapy (CET) would not be associated with improved survival relative to ET for patients with positive margins. MATERIALS AND METHODS: The National Cancer Database was queried for pathologic stage I HR + HER2-breast cancer patients treated with partial mastectomy and adjuvant whole-breast irradiation between 2004 and 2017. The adjuvant treatment approaches to positive surgical margins were investigated and compared. Overall survival was compared between systemic treatment groups using multivariable cox proportional hazards regression. RESULTS: Among 228,453 patients, a positive surgical margin (microscopic residual disease, R1) was identified in 3561 (1.6%) patients. Compared with complete resections, positive margin was associated with inferior overall survival (hazard ratio [HR] = 1.276, P = 0.003). Among the R1 patients, 78.7% received ET only, 11.7% received CET, 1.2% received chemotherapy only, and 8.5% received no systemic therapy. After controlling for patient, facility, and tumor characteristics, ET provided greatest survival benefit (relative to no therapy, HR = 0.378, P < 0.001) followed by CET (HR = 0.446, P = 0.020). Compared with ET alone, CET is not associated with additional overall survival benefit (HR = 1.179, P = 0.595). CONCLUSIONS: CET appeared not to be associated with an improved overall survival in early stage HR + HER2-breast cancer with microscopic residual disease relative to ET. Positive surgical margins therefore are probably not a relevant clinical factor for adjuvant chemotherapy decision-making.

Modeling the COVID Pandemic: Do Delays in Surgery Justify Using Stereotactic Radiation to Treat Low-Risk Early Stage Non-Small Cell Lung Cancer?

INTRODUCTION: It was suggested that stereotactic radiation (SBRT) is an "alternative if no surgical capacity is available" for non-small cell lung cancer (NSCLC) care during the COVID-19 pandemic. The purpose of this study was to compare the oncologic outcomes of delayed surgical resection and early SBRT among operable patients with early stage lung cancer. METHODS: The National Cancer Database was queried for patients with cT1aN0M0 NSCLC who underwent surgery or SBRT (2010-2016) with no comorbidity. Patients with any comorbidities or age >80 were excluded. The outcome of interest was overall survival. Delays in surgical care were modeled using different times from diagnosis to surgery. A 1:1 propensity match was performed and survival was analyzed using multivariable Cox regression. RESULTS: Of 6720 healthy cT1aN0M0 NSCLC patients, 6008 (89.4%) received surgery and 712 (10.6%) received SBRT. Among surgery patients, time to surgery >30 d was associated with inferior survival (HR > 1.4, P ≤ 0.013) compared with patients receiving surgery ≤14 d. Relative to SBRT, surgery demonstrated superior survival at all time points evaluated: 0-30 d, 31-60 d, 61-90 d, and >90 d (all P < 0.001). Among a propensity-matched cohort of 256 pairs of patients, delayed surgery (>90 d) remained association with better overall survival relative to early SBRT (5-year survival 76.9% versus 32.3%, HR = 0.266, P < 0.001). CONCLUSIONS: Although longer time to surgery is associated with inferior survival among surgery patients, delayed surgery is superior to early SBRT. Surgical resection should remain the standard of care to treat operable early stage lung cancer despite delays imposed by the COVID-19 pandemic.

A comparison of local therapy alone with local plus systemic therapy for stage I pT1aN0M0 HER2+ breast cancer: A National Cancer Database analysis.

BACKGROUND: Small invasive breast cancers (BCs) with tumor sizes ≤5 mm (T1a) are associated with an excellent prognosis without systemic therapy. Although HER2 overexpression (HER2+) is associated with a higher risk of recurrence and poorer clinical outcomes, in the absence of HER2 directed therapy, it remains unclear whether adjuvant systemic therapy is necessary in node-negative patients diagnosed with HER2+ invasive BCs ≤5 mm (pT1aN0M0). METHODS: The National Cancer Database was searched to identify patients diagnosed with HER2+ pT1aN0M0 BCs from 2004 to 2017. The cohort was stratified by treatment status: local therapy alone or local plus adjuvant systemic therapy. A 1:1 propensity match was performed. Overall survival (OS) was analyzed using stratified multivariable Cox proportional hazards regression analyses. RESULTS: Of the 8948 patients found, 4026 (45.0%) underwent surgery alone, and 4922 (55.0%) received surgery plus systemic therapy. Patients with either moderately differentiated (odds ratio [OR], 2.053; P < .001) or poorly/undifferentiated tumors (OR, 3.780; P < .001) or with the presence of lymphovascular invasion (OR, 3.351; P < .001) were more likely to have received systemic therapy. Propensity matching generated 1162 pairs of patients who were hormone receptor positive (HR+) and 748 pairs who were hormone receptor negative (HR-). Propensity matching effectively reduced selection bias between study groups. In the matched cohort, the addition of systemic therapy was not associated with superior OS (hazard ratio for HR+, 1.613; P = .107, and hazard ratio for HR- 1.319; P = .369) compared with patients who received local therapy alone. CONCLUSIONS: In pT1aN0M0 HER2+ BC, the addition of adjuvant systemic therapy after surgical excision was not associated with improved OS compared with local therapy alone.

Adjuvant trastuzumab with or without chemotherapy in stage 1 pT1N0 HER2+ breast cancer: a National Cancer Database analysis.

PURPOSE: Approximately 20% of all breast cancers (BC) are HER2 amplified. In the APT trial, weekly paclitaxel/trastuzumab in node negative HER2+ BC with tumors < 3 cm was associated with a 7-year invasive disease-free survival of 93%. However, this was in the context of a non-randomized trial, and for pT1N0 HER2+ BC it remains unclear whether HER2 monotherapy would provide similar clinical outcomes to chemo-HER2 therapy. We hypothesized that adjuvant chemo-HER2 therapy would be associated with a modestly improved overall survival compared to HER2 monotherapy in patients with tumors < 2 cm. METHODS: In the National Cancer Database (2004-2017), patients with a primary diagnosis of pT1N0M0 HER2+ BC, were separated into two groups: (i) HER2 monotherapy, i.e., trastuzumab, and (ii) chemo-HER2 therapy. A 3:1 propensity match was performed to balance patient selection bias between the two different cohorts. Long-term overall survival (OS) was compared between both groups. RESULTS: A total of 23,281 patients met the criteria. 22,268 (96.7%) received chemo-HER2 therapy and 1013 (4.4%) received HER2 monotherapy. Propensity match identified 1995 patients who received chemo-HER2 therapy, and 666 who received HER2 monotherapy. After matching, adjuvant chemo-HER2 therapy was associated with a modest survival advantage over HER2 monotherapy (5-year OS 94.1% vs. 90.6%, P = 0.041). CONCLUSIONS: Even though there is a modest OS advantage favoring adjuvant chemo-HER2 therapy in patients with pT1N0 HER2+ BC, HER2 monotherapy was associated with 5-year OS > 90%. Therefore, in select patients who have contraindications for cytotoxic chemotherapy, or decline adjuvant chemotherapy altogether, adjuvant trastuzumab monotherapy appears to be a reasonable alternative.

Guideline-Consistent Treatment for Inflammatory Breast Cancer Provides Associated Survival Benefit Independent of Age.

BACKGROUND: Guideline-consistent treatment (GCT) for inflammatory breast cancer (IBC) includes neoadjuvant chemotherapy (NAC), modified radical mastectomy (MRM), and radiation. We hypothesized that younger patients more frequently receive GCT, resulting in survival differences. METHODS: Using the National Cancer Database (2004-2018), female patients with unilateral IBC (by histology code and clinical stage T4d) were stratified by age (< 50, 50-65, > 65 years). Factors associated with NAC, MRM, radiation, and "GCT" (defined as all three treatments) were identified using multivariable logistic regression. Multivariable Cox proportional hazards regression identified predictors of overall survival. RESULTS: Of 3278 IBC patients, 30% were younger than 50 years, 44% were 50-65 years of age, and 26% were older than 65 years. The youngest group comprised the greatest proportion of non-White patients ([35%] vs. [29%] age 50-65 years and [23%] age > 65 years, p < 0.001) and was most often treated at academic facilities ([33%] vs. [28%] age 50-65 years; and [23%] age > 65, p < 0.001). Patients older than 65 years received NAC, MRM, and radiation less frequently, and only 35% underwent GCT (vs. [57%] age 50-65 years and [52%] age < 50 years; p < 0.001). On multivariable logistic regression, age older than 65 years independently predicted omission of NAC (odds ratio [OR], 0.36), MRM (OR, 0.56), and radiation (OR, 0.56) (all p < 0.001), and patients older than 65 years also were less likely to undergo GCT than patients 50-65 years of age (OR, 0.65; p = 0.001). GCT was associated with superior overall survival in all three age groups ([hazard ratio {HR}, 0.61] age < 50 years, [HR, 0.62] age 50-65 years, [HR, 0.53] age > 65 years; all p < 0.001). CONCLUSION: Advanced age alone should not limit receipt of GCT for IBC. Multimodal care should be performed for IBC patients of all ages to improve oncologic outcomes for this aggressive breast cancer subtype.

Neoadjuvant Endocrine Therapy as an Alternative to Neoadjuvant Chemotherapy Among Hormone Receptor-Positive Breast Cancer Patients: Pathologic and Surgical Outcomes.

BACKGROUND: Neoadjuvant chemotherapy (NCT) is considered more effective in downstaging hormone receptor-positive (HR+) breast cancer than neoadjuvant endocrine therapy (NET), particularly in node-positive disease. This study compared breast and axillary response and survival after NCT and NET in HR+ breast cancer. METHODS: Based on American College of Surgeons Oncology Group (ACOSOG) Z1031 criteria, women age 50 years or older with cT2-4 HR+ breast cancer who underwent NET or NCT and surgery were identified in the National Cancer Database 2010-2016. Chi-square and logistic regression analysis determined differences between the NCT and NET groups and therapy response, including downstaging and pathologic complete response (pCR, ypT0/is and ypN0). RESULTS: Of 19,829 patients, 14,025 (70.7%) received NCT and 5804 (29.3%) received NET. The NET patients were older (mean age, 68.9 vs. 60.3; P < 0.001) and had greater comorbidity (1+ Charlson-Deyo score, 21% vs. 16%; P < 0.001). Therapy achieved T downstaging (any) for 58% of the patients with NCT versus 40.5% of the patients with NET, and in-breast pCR was achieved for 9.3% of the NCT versus 1.3% of the NET patients (P < 0.001). Approximately half of the mastectomy procedures could have been potentially avoided for the patients with in-breast pCR (53.6% of the NCT and 43.8% of the NET patients). For the cN+ patients, N downstaging (any) was 29% for the NCT patients versus 18.3% for the NET patients (P < 0.001), and nodal pCR was achieved for 20.3% of the NCT versus 13.5% of the NET patients (P < 0.001). Among those with nodal pCR, axillary lymph node dissection (ALND) still was performed for 56% of the patients after NCT and 45% of the patients after NET. CONCLUSIONS: Although the response rates after NCT were higher, NET achieved both T and N downstaging and pCR. Neoadjuvant endocrine therapy can be used to de-escalate surgery for patients who cannot tolerate NCT or when chemotherapy may not be effective based on genomic testing.

Despite Equivalent Outcomes, Men Receive Neoadjuvant Chemotherapy Less Often Than Women for Lymph Node-Positive Breast Cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) downstages breast cancer and provides prognostic information. Males with breast cancer are known to receive less treatment overall and have poorer outcomes relative to females. We hypothesized that males would be less likely to receive NAC. PATIENTS AND METHODS: Patients with a primary diagnosis of cN1-3 breast cancer were identified in the National Cancer Database (2004-2016). Multivariable logistic regression determined the association between NAC utilization and sex, and the relationship between sex and NAC response, controlling for demographic and tumor factors. Overall survival was analyzed using a multivariable Cox model. RESULTS: In total, 196,027 patients (194,010 females, 2017 males) met inclusion criteria. A significantly greater proportion of males underwent mastectomy (80% vs. 60%, P < 0.001), and axillary lymph node dissection (76% vs. 74%, P = 0.022). Overall fewer men received chemotherapy than women (73% vs. 84%, P < 0.001); men also received NAC at a significantly lower rate (26% men vs. 45% women, P < 0.001). After accounting for demographic and oncologic factors including hormone receptor (HR) subtype, females remained more likely to undergo NAC (OR 1.84, P < 0.001). On multivariable analysis, sex was not associated with pathologic response or overall survival after NAC. CONCLUSIONS: Although oncologic outcomes after NAC were similar, males with node-positive breast cancer received less NAC and more aggressive surgery than females. These data suggest men achieve outcomes comparable to women with cN1-3 disease, and NAC should be used in appropriate male patients to downstage the breast and axilla.

Hospital System Adoption of Magnetic Seeds for Wireless Breast and Lymph Node Localization.

BACKGROUND: As an alternative to traditional wire localization, an inducible magnetic seed system can be used to identify and remove nonpalpable breast lesions and axillary lymph nodes intraoperatively. We report the largest single-institution experience of magnetic seed placement for operative localization to date, including feasibility and short-term outcomes. METHODS: Patients who underwent placement of a magnetic seed in the breast or lymph node were identified from July 2017 to March 2019. Imaging findings, core needle biopsy, surgical pathology results, and type of surgery were collected. Outcomes included procedural complications, magnetic seed and biopsy clip retrieval rates, and need for additional surgery. RESULTS: A total of 842 magnetic seeds were placed by nine radiologists in 673 patients and retrieved by six surgeons at six operative locations. The majority of breast lesions were malignant (395/659, 59.9%); 136 seeds were placed for lymph node localization. The overall magnetic seed retrieval rate was 98.6%, whereas the biopsy clip retrieval rate was 90.9%. Only six patients (0.7%) experienced a complication from magnetic seed placement. Reexcision was performed in 15.2% of patients with breast cancer; 9.6% of benign/high risk lesions were upgraded to malignancy at surgical excision. CONCLUSIONS: The magnetic seed technique is safe, effective, and accurate for localization of breast lesions and lymph nodes, and importantly uncouples surgery from the localization procedure. The high magnetic seed retrieval rate and low reexcision rate may reflect the accuracy of magnetic marker placement as a "second chance" localization procedure, especially in cases with biopsy clip migration.

Improving the Accuracy of Axillary Lymph Node Surgery in Breast Cancer with Ultrasound-Guided Wire Localization of Biopsy Proven Metastatic Lymph Nodes.

BACKGROUND: This study aimed to evaluate whether the use of preoperative ultrasound (US)-guided wire localization of metastatic axillary lymph nodes (LN) assessed previously by core needle biopsy (CNB) and clip placement in breast cancer patients improves successful surgical removal. METHODS: A retrospective review examined breast cancer patients who underwent US-guided CNB of an axillary LN and biopsy clip placement as well as axillary lymph node dissection (ALND) or sentinel node lymph node biopsy (SLNB) from 1 January 2010 to 30 September 2013. Preoperative needle localization status, neoadjuvant chemotherapy, and type of axillary LN surgery were reviewed. Confirmation that the metastatic LN had been surgically removed was determined on the specimen image, by pathologic report confirmation, or by pre-radiation therapy computed tomography (CT) scan. RESULTS: Preoperative US-guided needle localization was performed for 68.2 % (73/107) of the patients, with 97.3 % (n = 71) demonstrating confirmation of biopsy clip and LN removal versus 79.4 % (n = 27) of the 34 patients showing no performance of needle localization (p = 0.0043). Subgroup analysis showed a significant difference in removal of metastatic LN between the patients who received neoadjuvant chemotherapy [97 % of LNs removed with wire localization (n = 65/67) vs. 83.3 % of LNs removed without wire localization (n = 20/24; p = 0.04)] and the patients who had ALND, [96.3 % of LNs removed with wire localization (n = 52/54) vs. 77.8 % of LNs removed without wire localization (n = 21/27; p = 0.015)]. CONCLUSION: US-guided wire localization of metastatic axillary LNs that have had biopsy with clip placement significantly improves the success rate of surgical removal, allowing more accurate staging and decreasing the false-negative rates of SLNB after neoadjuvant therapy.

Using MammaPrint on core needle biopsy to guide the need for axillary staging during breast surgery.

BACKGROUND: At present, the only opportunity to omit axillary staging is with Choosing Wisely criteria for women ages >70 y with cT1 2N0 estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer. However, many women are diagnosed when pathologic node status-negative, raising the question of additional opportunities to omit sentinel lymph node biopsy. We sought to investigate the association between MammaPrint, a genomic test that estimates estrogen receptor-positive breast cancer recurrence risk, and pathologic node status, with the aim that low-risk MammaPrint could be considered for omission of sentinel lymph node biopsy if associated with pathologic node status-negative. METHODS: A single-institution database was queried for all women with cT1 2N0 estrogen receptor-positive/human epidermal growth factor receptor 2-negative invasive breast cancer with breast surgery as their first treatment and MammaPrint performed from 2020 to 2021. Patient and tumor factors, including MammaPrint score, were compared with axillary node status for correlation. RESULTS: A total of 668 women met inclusion criteria, with a median age of 66 y. MammaPrint was low-risk luminal A in 481 (72%) and high-risk luminal B in 187 (28%). At the time of breast surgery, 588 (88%) had sentinel lymph node biopsy, 27 (4%) had axillary lymph node dissection, and 53 (7.9%) had no axillary staging. Most women in both the pathologic node status-negative and pathologic node status-positive cohorts had low-risk MammaPrint (355 [73.3%] pathologic node status-negative vs 91 [69.5%] pathologic node status-positive), and women with low-risk MammaPrint did not have a significantly lower risk of pathologic node status-positive (P = .377). CONCLUSION: Low-risk MammaPrint does not predict lower risk of pathologic node status-positive breast cancer. Based on our results, genomic testing does not appear to provide additional personalization for the ability to omit sentinel lymph node biopsy for patients outside of the Choosing Wisely guidelines.

Should breast surgery be considered for patients with de novo metastatic inflammatory breast cancer?

INTRODUCTION: We aimed to identify factors predicting surgery for de novo stage IV inflammatory breast cancer (IBC) and determine the association of surgery with overall survival (OS). METHODS: Female patients with unilateral AJCC clinical stage IV IBC treated 2010-2018 in the NCDB were identified. Logistic regression and multivariable proportional Cox hazards regressions determined factors associated with treatment and OS. RESULTS: Of 1049 patients, 29.1% underwent breast surgery (BS) and 70.9% had no surgery (NS). Increasing age and more recent treatment year were significantly associated with NS. 2-Year OS was superior in BS patients (71% vs 38% NS). Single-site and bone-only metastasis had no association with treatment type or OS. CONCLUSION: Contrary to guidelines, 1/3 of de novo stage IV IBC patients underwent BS, and had an independent OS benefit irrespective of extent or site of metastasis. Further research is needed to determine which patients with stage IV IBC should undergo BS.

Trends in surgery and survival for T1-T2 male breast cancer: A study from the National Cancer Database.

BACKGROUND: Despite evidence that early-stage male breast cancer (MBC) can be treated the same as in females, we hypothesized that men undergo more extensive surgery. METHODS: Patients with clinical T1-2 breast cancer were identified in the National Cancer Database 2004-2016. Trends in surgery type and overall survival were compared between sexes. RESULTS: Of 9,782 males and 1,078,105 females, most were cN0 with AJCC stage I/II disease. Unilateral mastectomy was most common in men (67.1% vs. 24.1%, p < 0.001) and partial mastectomy in women (64.7% vs. 26.4%, p < 0.001), with no significant change over time. Over 1/3 of men received ALND in 2016. While overall survival was superior in females (HR 0.83, 95% CI 0.73-0.94, p = 0.003), partial mastectomy was associated with a 42% reduction in mortality risk for males (HR 0.58, 95% CI 0.4-0.8, p = 0.003). CONCLUSIONS: De-escalation of surgery could be considered for MBC to improve survival and align with current standards of care.

Minimally Invasive Mastectomy Could Achieve Non-inferior Oncological Outcome in Appropriately Selected Patients: Propensity Matched Analysis of the National Cancer Database.

BACKGROUND: Minimally invasive mastectomy (MIM) was emerged as an approach to decrease morbidity and increase patient satisfaction through improved cosmetic results; however, there is a paucity of data regarding the long-term oncologic outcomes of these minimally invasive approaches. METHODS: Patients who underwent mastectomy procedures were identified in the National Cancer Database (2010-2016). Patients were categorized as MIM or open mastectomy. A 1:1 propensity match was performed to balance the bias on reconstruction, nipple sparing, lymph node procedures, and other confounding factors between the cohorts. Short- and long-term outcomes were compared. RESULTS: A total of 328 811 patients met the criteria: 327 643 (99.6%) received open mastectomy and 1168 (.4%) received MIM. Propensity match identified 384 "pairs" of MIM and open mastectomy patients. Among them, MIM was associated with shorter length of stay (LOS) (mean 1.3 vs. 1.06 days, P = .003). No differences were observed in the rates of positive margins, unplanned readmissions, or 90-day mortality between the 2 operative approaches. Overall survival (OS) was equivalent between MIM and open mastectomy patients. Cox proportional hazard regression showed no effect of the procedure performed on OS. DISCUSSION: MIM is associated with shorter LOS, and it is non-inferior to open mastectomy in terms of other short-term outcomes and long-term oncologic survival outcomes. These data suggest that MIM may be considered in appropriately selected breast cancer patients as an additional approach to the community.

Partial Breast Reirradiation for Patients With Ipsilateral Breast Tumor Recurrence After Initial Treatment With Breast Conservation for Early Stage Breast Cancer.

PURPOSE: Accelerated partial breast irradiation (APBI), including intraoperative radiation therapy (IORT), is an evidence-based treatment option in patients undergoing breast conserving surgery (BCS) for early-stage breast cancer. However, literature regarding reirradiation for patients with ipsilateral breast tumor recurrences (IBTR) is limited. This prospective study assessed the feasibility and efficacy of using APBI in patients who had prior whole breast irradiation. METHODS AND MATERIALS: This was a single institution, prospective study of patients who were previously treated with BCS and adjuvant whole breast radiation. At the time of enrollment, all had unifocal IBTR, histologically confirmed invasive ductal carcinoma with negative margins after repeat BCS. Patients received either IORT in a single fraction at time of BCS or MammoSite brachytherapy twice daily over 5 days. Follow-up data and patient surveys were collected at 1, 3, 6, 9, and 12 months, then annually for at least a 5-year period. RESULTS: From 2008 to 2014, 13 patients were enrolled. Median time to recurrence after initial course of radiation was 12.5 years. Median follow-up after retreatment was 7.8 years. One patient in the IORT group had a subsequent tumor bed recurrence, yielding a local control of 92%. One patient had distant recurrence. At baseline, 680 reported excellent-good cosmesis compared with 42% at 5 years. All patients indicated total satisfaction with overall treatment experience. CONCLUSIONS: APBI using IORT was well tolerated with excellent local control and may be a reasonable alternative to mastectomy for IBTR. Further study is needed to determine the most suitable candidates for this approach.

Age disparities in triple-negative breast cancer treatment and outcomes: An NCDB analysis.

BACKGROUND: Race, access to care, and molecular features result in outcome disparities in triple-negative breast cancer (TNBC). We sought to determine the role of age in TNBC disparity by hypothesizing that younger patients receive more comprehensive treatment, resulting in survival differences. METHODS: The National Cancer Database was used to identify women with unilateral TNBC treated from 2005 through 2017. Patients were stratified by age (≤40, 41-70, >70); demographics, clinical characteristics, and treatment factors were compared. Logistic regression determined factors associated with treatment received. Survival outcomes were analyzed using a stratified log-rank test. RESULTS: Of the 168,715 patients, 16,287 (9.6%) were ≤40 years. Patients ≤40 were significantly more likely to present at higher clinical stage (P < .001) and receive neoadjuvant chemotherapy (NAC, P < .001). Bilateral mastectomy was the most common surgery for patients ≤40 (37%), whereas partial mastectomy was most often used in patients 41 to 70 years old (48%) and those >70 (49%) (P < .001). Patients ≤40 years were significantly more likely to undergo both NAC and mastectomy than those >40 (odds ratio 1.5, both P < .05) despite a greater in-breast tumor response in the youngest patients. Patients treated with mastectomy and axillary lymph node dissection had inferior survival outcomes compared to those treated with partial mastectomy and sentinel lymph node biopsy across all 3 age groups (P < .001). CONCLUSION: The clinical characteristics of TNBC differ significantly at the extremes of age, likely driving treatment decisions. Although patients ≤40 present with a more advanced disease and appropriately receive NAC, they also undergo more extensive surgery that does not yield a survival benefit. Further research is needed to determine if age disparity is due to oncologic factors or patient and provider preferences.

A vasculature-targeting regimen of preoperative docetaxel with or without bevacizumab for locally advanced breast cancer: impact on angiogenic biomarkers.

PURPOSE: Taxanes have effects on angiogenesis causing difficulties in separating biological effects of chemotherapy from those due to angiogenesis inhibitors. This randomized phase II trial was designed to evaluate the additional biomarker effect on angiogenesis when bevacizumab is added to docetaxel. EXPERIMENTAL DESIGN: Patients with inoperable breast cancer were randomized to either 2 cycles of preoperative docetaxel (D) 35 mg/m(2) i.v. weekly for 6 weeks, followed by a 2-week break; or docetaxel with bevacizumab 10 mg/kg i.v. every other week for a total of 16 weeks (DB). Plasma and serum markers of endothelial damage, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and tumor microvessel density were assessed before treatment and at the end of each preoperative cycle. RESULTS: Forty-nine patients were randomized (DB, 24; D, 25). There was no difference in overall clinical response, progression-free survival, or overall survival. Vascular endothelial growth factor increased during treatment; more so with DB (P < 0.0001). Vascular cell adhesion molecule-1 (VCAM-1) also increased (P < 0.0001); more so with DB (P = 0.069). Intercellular adhesion molecule increased (P = 0.018) and E-selectin decreased (P = 0.006) overall. Baseline levels of VCAM-1 and E-selectin correlated with clinical response by univariate analysis. DCE-MRI showed a greater decrease in tumor perfusion calculated by initial area under the curve for the first 90 seconds in DB (P = 0.024). DCE-MRI also showed an overall decrease in tumor volume (P = 0.012). CONCLUSION: Bevacizumab plus docetaxel caused a greater increase in vascular endothelial growth factor and VCAM-1, and a greater reduction in tumor perfusion by DCE-MRI compared with docetaxel. Clinical outcomes of inoperable breast cancer were predicted by changes in VCAM-1 and E-selectin.