My name is Rodrigo Arrangoiz I am a breast surgeon/ thyroid surgeon / parathyroid surgeon / head and neck surgeon / surgical oncologist that works at Center for Advanced Surgical Oncology in Miami, Florida.
I was trained as a surgeon at Michigan State University from (2005 to 2010) where I was a chief resident in 2010. My surgical oncology and head and neck training was performed at the Fox Chase Cancer Center in Philadelphia from 2010 to 2012. At the same time I underwent a masters in science (Clinical research for health professionals) at the University of Drexel. Through the International Federation of Head and Neck Societies / Memorial Sloan Kettering Cancer Center I performed a two year head and neck surgery and oncology / endocrine fellowship that ended in 2016.
Mi nombre es Rodrigo Arrangoiz, soy cirujano oncólogo / cirujano de tumores de cabeza y cuello / cirujano endocrino que trabaja Center for Advanced Surgical Oncology en Miami, Florida.
Fui entrenado como cirujano en Michigan State University (2005 a 2010 ) donde fui jefe de residentes en 2010. Mi formación en oncología quirúrgica y e n tumores de cabeza y cuello se realizó en el Fox Chase Cancer Center en Filadelfia de 2010 a 2012. Al mismo tiempo, me sometí a una maestría en ciencias (investigación clínica para profesionales de la salud) en la Universidad de Drexel. A través de la Federación Internacional de Sociedades de Cabeza y Cuello / Memorial Sloan Kettering Cancer Center realicé una sub especialidad en cirugía de cabeza y cuello / cirugia endocrina de dos años que terminó en 2016.
The Meta-Analysis of Chemotherapy in Head and Neck Cancer (MACH-NC):
Is an individual patient data analysis intended to evaluate the role of chemotherapy in head and neck cancers
It is known for its rigorous process for quality data collection and its large ongoing data- base
Results of indirect comparisons were not limited to evaluation of survival advantage:
But an estimate of the interaction between the treatment effects and the timing of chemotherapy as adjuvant, concurrent, neoadjuvant, or induction was made possible (Pignon and Bourhis, 1995 Oct)
Since the first reports of MACH-NC:
Results demonstrated an:
8.6% benefit of cause-specific survival (CSS) at 5 years, hazard ratio, 0.81; 95% CI, 0.78–0.86; P = 0.001):
For concurrent chemoradiation (CCRT):
While systemic chemotherapy in the setting of induction or adjuvant did not show OS advantage
Nevertheless, the magnitude of the overall response rate of induction chemotherapy (IC) with the PF regimen (cisplatin 100 mg/m2 on day 1 and 5-fluorouracil 1000 mg/m2 daily for 5 days):
Was high and ranged from 57% to 80%, with a complete response rate of 19% to 48%
Analyses on the subset of 15 trials who received PF:
Showed a modest improvement in OS compared to CCRT (HR, 0.90; 95% CI, 0.82–0.99):
Which is a survival gain equal to 5% at 5 years
In the MACH-NC a subset analysis of 16 IC trials with non-PF combinations:
Did not show survival benefit with these IC regimens:
Which is attributed to the low dose of ineffective regimens that were administered for a duration not long enough:
Here, PF showed more adequate responses in comparison with non-PF trials:
Which reflects the nature of PF as a more potent drug combination for the most common administered schedules (Pignon et al., 2009; Monnerat et al., 2002):
So, in particular PF became the dominant induction regimen for years
The standard of care with respect to surgical management of early stage breast cancer with a clinically negative axilla:
Is to undergo axillary staging with sentinel lymph node biopsy (SLNB)
In patients who are clinically node negative undergoing lumpectomy with SLNM and SLNB:
A completion axillary lymph node dissection (ALND) is not required if one or two lymph nodes are positive:
These patients should go on to receive adjuvant therapy:
Omission of ALND does not lead to a difference in 10-year locoregional recurrence or overall survival
There is, however, a role for omission of axillary staging in elderly women:
Who are clinically node negative with ER+ tumors:
Particularly if co-morbidities are present
The Cancer and Leukemia Group B (CALBG) 9343 study:
Evaluated women ≥ 70 years of age who underwent lumpectomy:
For clinical T1, N0, ER+ breast cancer +/- adjuvant radiation (RT):
With tamoxifen (Tam) recommended for all patients
Of the 636 participants:
404 (64%) did not undergo any initial axillary surgery
At 12-year follow-up:
There were no axillary recurrences among women who underwent initial axillary dissection
Among those who did not undergo axillary dissection:
There were no axillary recurrences:
In the Tam + RT group
Six of 200 in the Tam group (3%) had axillary recurrences
The International Breast Cancer Study Group Trial 10-93:
Evaluated 473 patients with early stage breast cancer who were clinically node negative
Patients had a mean age of 74
The majority of patients were ER+, and patients were randomized to breast surgery +/- axillary dissection followed by endocrine therapy
Overall, 2% of patients had an axillary recurrence (1% of those with axillary surgery vs. 3% in patients without axillary surgery):
With no difference in disease-free and overall survival.
Results from these and other studies recently led the Society of Surgical Oncology to release the Choosing Wisely guidelines:
Recommending against routine use of SLNB in clinically node-negative women ≥70 years of age with hormone positive cancer:
Hormonal therapy is typically recommended for patients with hormone receptor positive disease
Omission of SLNB in clinically node-negative women ≥70 years of age treated with hormonal therapy does not result in a significantly increased rate of locoregional recurrence and does not impact breast cancer mortality:
Thus, although axillary staging with SLNB continues to be the standard of care:
Omission of axillary staging can be considered in some patients ≥70 years of age with:
Early stage, clinically node-negative, hormone receptor positive breast cancer
References
Giuliano AE, Ballman K, McCall L, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: long-term follow-up from the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 randomized trial. Ann Surg. 2016;264(3):413-420.
Giuliano AE, Ballman KV, McCall L, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (Alliance) Randomized Clinical Trial. JAMA. 2017;318(10):918-926.
Hughes KS, Schnaper LA, Bellon JR, et al. Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343. J Clin Oncol. 2013;31(19):2382-2387.
International Breast Cancer Study Group: Randomized trial comparing axillary clearance versus no axillary clearance in older patients with breast cancer: first results of International Breast Cancer Study Group Trial 10-93. J Clin Oncol.2006;24(3):337-344.
Has been a longstanding standard of care for hormone receptor–positive breast cancer:
In both the early and advanced stages
In more recent years, endocrine therapy combined with a CDK4/6 inhibitor:
Has become the first-line standard of care for most women with hormone receptor–positive, HER2 negative metastatic breast cancer (MBC)
Use of first-line endocrine therapy plus a CDK4/6 inhibitor is based on positive results from several clinical trials:
The hazard ratios for progression-free survival (PFS) were very similar in these trials
Recently, statistically significant improvements in overall survival were reported in multiple phase 3 studies of ribociclib plus endocrine therapy:
For example, the secondary end point of overall survival (OS) was met in the MONALEESA-2 study of ribociclib plus an aromatase inhibitor
Of note, at the second interim analysis of data from the phase 3 MONARCH-3 clinical trial of abemaciclib plus endocrine therapy, OS data remained immature (HR, 0.754; 95% CI, 0.584-0.974; P = 0.03)
The addition of palbociclib to letrozole in the PALOMA-2 study of did not yield a statistically significant benefit in terms of OS (HR, 0.956; 95% CI, 0.777–1.177):
PALOMA-2 study investigators noted that final OS data were missing for 13% in the experimental arm vs 21% in the control arm
The safety and efficacy of olaparib as adjuvant therapy was evaluated in the phase 3 OlympiA trial:
That enrolled patients with a germline BRCA mutationand HER2-, high-risk, early-stage breast cancer who had completed definitive local treatment and at least 6 cycles of neoadjuvant or adjuvant chemotherapy containing anthracyclines, a taxane, or both (prior platinum for previous cancer or as adjuvant /neoadjuvant breast cancer treatment was permitted)
Patients were randomly assigned (1:1) to receive:
Olaparib tablets 300 mg orally twice daily or placebo
Treatment was continued for up to 1 year or until disease recurrence or unacceptable toxicity occurred
In this study, patients with high-risk, early breast cancer were identified using the following criteria:
Patients who received prior neoadjuvant chemotherapy:
Triple-negative breast cancer (TNBC):
They needed to have residual invasive cancer in the breast and / or the resected lymph nodes (nonpathologic complete response) at the time of surgery
Hormone receptor–positive breast cancer:
They needed to have residual invasive cancer in the breast and / or the resected lymph nodes (nonpathologic complete response) at the time of surgery:
Additionally, they needed a score of 3 or more based on pretreatment clinical and post-treatment pathologic stage, ER status, and histologic grade (Table)
Patients who received prior adjuvant chemotherapy:
TNBC:
They needed to have node-positive disease or node-negative disease with the primary tumor measuring 2 cm or more
Hormone receptor–positive, HER2- breast cancer:
They needed to have 4 or more pathologically-confirmed positive lymph nodes
Early Breast Cancer Stage, Receptor Status, and Grade Scoring Requirements for OlympiA Enrollment.
Updated results, representing a median follow up of 3.5 years, were published in October 2022:
A significant improvement in OS was observed in the olaparib group compared to the placebo group:
HR, 0.68; 98.5% CI, 0.47-0.97; P = 0.009:
Four-year OS rates were 89.8% with olaparib and 86.4% with placebo
Continued benefit in terms of invasive disease free survival (IDFS) and distant DFS (DDFS) were demonstrated with olaparib versus placebo
In subset analyses, OS, IDFS, and DDFS benefits were observed across major subgroups
At updated analysis, the safety findings were consistent with what had been reported previously:
Adverse events (AEs) associated with adjuvant abemaciclib are considered manageable and acceptable in this patient population
The most common AEs reported (≥ 20%) in the abemaciclib plus endocrine therapy arm and at least 2% higher than in the endocrine therapy–alone arm were:
Diarrhea, infections, neutropenia, fatigue, leukopenia, nausea, anemia, and headache
The most frequently reported (≥ 5%) grade 3 or 4 AEs were:
Neutropenia, leukopenia, diarrhea, and lymphopenia
Clinicians should be aware of the potential for certain rare, but serious, toxicities:
For patients with early-stage breast cancer, gene expression assays can be used to determine the likelihood of recurrence and the potential benefit of adjuvant chemotherapy
For example, the Oncotype Dx assay, which is based on the expression profile of 21 genes, provides a score (ie, recurrence score) that is both prognostic and predictive of chemotherapy benefit
Node-negative tumors with a recurrence score of 0 to 10 have a very good prognosis, with a low rate of distant recurrence at 10 years
Conversely, tumors with a high recurrence score (> 25) have higher risk for recurrence and have been shown to benefit from chemotherapy in retrospective studies
In the TAILORx studies, postmenopausal patients with node-negative, HR+ early breast cancer and intermediate recurrence score (11 to 25) did not derive a significant benefit from chemotherapy, which is thus not recommended for this subgroup of patients
Most women don’t have any symptoms at diagnosis of breast cancer, which typically follows abnormalities at breast imaging detected through screening programs
However, approximately 1 in 6 women with breast cancer present with symptoms other than a breast lump
Of note, women with non-lump breast symptoms often delay seeking help, which is concerning as longer intervals to diagnosis have been associated with lower survival rates
In the United States, approximately 6% of tumors are metastatic at presentation, which not rarely are diagnosed in patients with neglected tumors