NATALEE was designed to evaluate the combination of ribociclib plus endocrine therapy in patients with early breast cancer
There was a trend toward improved OS with ribociclib plus endocrine therapy, and a 3-year treatment duration of ribociclib 400 mg showed a predictable safety profile that was more favorable than the 600 mg dose of ribociclib used in the metastatic setting
Follow-up data is still being collected, and further quality-of-life results will be provided later in the year
The combination of CDK 4 / 6 inhibitor ribociclib plus endocrine therapy significantly improved invasive disease-free survival (iDFS) compared with endocrine therapy alone in a broad population of patients with stage II or III HR-positive /HER2-negative early breast cancer:
According to results of the second interim efficacy analysis of the phase 3 NATALEE study
With a median follow-up for iDFS of 27.7 months:
The risk for invasive disease was reduced by 25.2% with ribociclib plus endocrine therapy compared with endocrine therapy alone (HR 0.748, 95% CI [0.618, 0.906]; P = .0014)
The 3-year iDFS rate was 90.4% for the combination therapy compared with 87.1% for endocrine therapy alone:
Which is an absolute difference of 3.3%
These results support ribociclib plus endocrine therapy as a new and effective treatment of choice for a broad population of at-risk patients with stage II or III HR-positive / HER2-negative early breast cancer, which is easy to identify in clinical practice
A 61-year-old woman presented to the hospital with dysphagia to solid foods and dyspnea on exertion that has been worsening over the last 1-2 months. Past medical history includes hypothyroidism from Hashimoto’s thyroiditis on levothyroxine, and T2DM on metformin (well-controlled). Physical exam is notable for significant diffuse thyroid enlargement, not rock hard or tender thyroid, positive Pemberton’s sign, hoarse voice (but she is able to speak in full sentences). Biochemical testing revealed normal CBC, CMP, and a TSH of 5.02 uIU/mL (normal 0.5-5.7). Thyroid ultrasound and neck CT are shown below.
What Is the Most Likely Cause for This Finding?
Anaplastic thyroid carcinoma
Fibrous thyroiditis
Subacute thyroiditis
Diffuse large B-cell lymphoma
Mucosa-associated lymphoid tissue (MALT) lymphoma
Correct Answer: Diffuse large B-cell lymphoma
This patient, with a history of Hashimoto’s thyroiditis, presents with a rapidly enlarging thyroid mass that has caused dysphagia and dyspnea on exertion. In that clinical context, the most likely etiology of her symptoms is thyroid lymphoma, and the most common type of primary thyroid lymphoma is diffuse large B-cell lymphoma (DLBCL). Thyroid lymphoma is a rare malignancy representing less than 5% of all thyroid cancers. Hashimoto’s thyroiditis is a well-established risk factor, as patients with Hashimoto’s thyroiditis have a 60 times higher risk of developing primary thyroid lymphoma, compared to the general population. On ultrasound, thyroid lymphoma will appear with diffuse enlargement of the thyroid in a uniform and very hypoechoic pattern, like the one presented here. Usually cross-sectional imaging will be needed, and in this case, there was the apparent narrowing of the upper trachea.
DLBCL usually appears malignant on cytology, while MALT lymphoma can be more subtle, which might result in an Atypia of Undetermined Significance (AUS) by the Bethesda classification. If lymphoma is clinically suspected, it is very important to obtain material for flow cytometry with the biopsy. Treatment of thyroid lymphomas depends on the subtype and staging of the tumor. Usually R-CHOP (rituximab- cyclophosphamide, doxorubicin, vincristine, prednisolone) is used, and no thyroidectomy is recommended.
This patient did not appear to demonstrate hyperthyroidism, nor had a tender thyroid gland, so subacute thyroiditis is unlikely. Fibrous thyroiditis (or Riedel’s thyroiditis) will present with a very hard, fixed goiter. Anaplastic thyroid carcinoma would usually present with asymmetric enlargement of the thyroid, as there is usually a dominant nodule that does not involve the thyroid gland in its entirety
The Breast Cancer Index (BCI) and BCI node-positive (BCIN+) risk scores are effective at estimating the individual risk of overall and late distant recurrent (DR) breast cancer, including in HR-positive early breast cancer, according to research from the ASCO 2023 Annual Meeting.
The researchers calculated the BCI /BCIN+ continuous risk scores for 1,285 patients with non-invasive cancer (group N0) and 1,762 patients with breast cancer spread to 1-3 lymph nodes or in internal mammary lymph nodes (group N1). They evaluated the hazard ratios and confidence intervals for BCI/BCIN+ continuous risk scores after adjusting for factors such as age, size of tumor, grade, and treatment.
They estimated the 10-year risk of overall recurrence as well as risk of late DR (between 5 years and 10 years).
In patients who did not undergo adjuvant chemotherapy and for patients who were DR-free at 5 years, the researchers evaluated overall and late DR continuous risk curves to reflect the two key time points for breast cancer treatment decision-making.
Concerning overall DR, BCI was significantly prognostic for patients in the N0 group (1,197 patients; HR = 1.39; 95% CI, 1.25-1.54; P < .001) as well as in the N1 group for patients who did not undergo chemotherapy (1,319 patients; HR = 4.29; 95% CI, 2.93-6.28; P < .001).
BCI was also significantly prognostic for late DR among patients in the N0 group (1,285 patients; HR = 1.23; 95% CI, 1.07-1.42; P < .001) and BCIN+ was prognostic in the N1 group (1,762 patients; HR = 2.78; 95% CI, 1.75-4.43; P < .001).
In a subset of patients with HER2-negative breast cancer, BCI/BCIN+ was prognostic for overall DR in the N0 group (978 patients; HR = 1.52; 95% CI, 1.34-1.73; P < .001) and N1 group (1,132 patients; HR = 4.04; 95% CI, 2.66-6.13; P < .001) as well as late DR in the N0 group (1,063 patients; HR = 1.31; 95% CI, 1.11-1.53; P < .001) and N1 group (1,503 patients; HR = 2.87; 95% CI, 1.17-4.81; P < .001).
Results from this largest BCI study to date further support the use of BCI to provide individualized risk estimates for both overall and late DR in women with HR+ breast cancer to aid in personalized decision-making for adjuvant therapy.
Rodrigo Arrangoiz MS, MD, FACS is a a cancer surgeon that specializes in BreastSurgery, Head and Neck Surgery, EndocrineSurgery, and ComplexOncology Surgery .
He graduated as a medical doctor (MD) from one of the top medical schools in Mexico called Anahuac University Suma Cum Laude.
He is an Assistant Professor at the Columbia University Division of Surgical Oncology at Mount Sinai Medical Center
Dr. Arrangoiz is an expert in managing thyroid cancer, benign thyroid diseases, primary hyperparathyroidism, breast diseases, breast cancer, skin cancer and Head and Neck Tumors.
He was trained in the best academic institutions in the United States and maintains certifications by the Board of General Surgery and Surgical Oncology in Mexico and the United States.
His training included:
General and Gastrointestinal Surgery – Michigan State University (2004 – 2010)
Oncological Surgery / Head and Neck Tumors / Endocrine Surgery –Fox Chase Cancer Center in Philadelphia (2010 to 2012)
Master of Science (Clinical Research for Health Professionals) –Drexel University (Philadelphia) (2010 – 2012)
Head and Neck Tumor Surgery / Endocrine Surgery (2014 to 2016) – IFHNOS / Memorial Sloan Kettering Cancer Center
He has participated in multiple courses and congresses as a Lecturer and Guest Professor, and has published multiple articles on topics related to his specialty.
He is certified by the Mexican Board of General Surgery and the Mexican Board of Oncology as well as one of the few Mexican physicians certified by, the AMERICAN BOARD OF SURGERY.
He is a member of various medical associations including the American College of Surgeons, American Thyroid Association, American Society of Endocrine Surgeons, American Medical Association, American Society of Clinical Oncology, Association of Academic Surgeons, Society of Surgical Oncology, The Society of Surgery of the Alimentary Tract, Society of American Gastrointestinal Endoscopic Surgeons,and the American Society of Breast Surgeons , among others.
Thanks to this, Dr. Rodrigo Arrangoiz is one of the most well respected Head and Neck surgeons in Mexico, in addition to being awarded as one of the 50 best doctors in Mexico in the Top Doctors Awards 2018 and Top Doctors Awards 2019.
Specialty:
Head and Neck Surgery
Thyroid and Parathyroid Surgery
Breast Surgery
Complex Surgical Oncology
Areas of Clinical Interest:
Malignant thyroid disease (papillary, follicular, medullary, anaplastic thyroid cancer, thyroid lymphoma, and metastatic disease to the thyroid gland) benign thyroid diseases (goiter, multinodular goiter, substernal goiter, hyperthyroidism), hyperparathyroidism / hypercalcemia, benign and malignant breast diseases, head and neck surgery and head and neck cancer.
Oral paclitaxel, carboplatin, and the PD-1 inhibitor dostarlimab in early triple-negative breast cancer
Among 56 patients with triple-negative breast cancer:
This combination therapy was found to be safe and moderately effective:
Demonstrating an estimated pathologic complete response rate of 48%
Results are preliminary:
Further investigation is needed before implementing in clinical practice
The phase 2 I-SPY2 trial found that patients with triple-negative breast cancer:
Who received the novel combination of oral paclitaxel, carboplatin, and the PD-1 inhibitor dostarlimab:
Demonstrated a higher predicted pathologic complete response (pCR) than control participants
Furthermore, drug-related adverse events from the novel combination treatment were manageable
I-SPY2 is the first trial to study combination therapy with oral paclitaxel, carboplatin, and the PD-1 inhibitor dostarlimab in early triple-negative breast cancer
The findings show that oral paclitaxel, carboplatin, and dostarlimab:
Can be effective in triple-negative breast cancer:
Although the estimated pCR rate of 48% is not as high as we anticipated for a triplet-therapy combination that includes a taxane, platinum chemotherapy, and an immune checkpoint inhibitor in this subgroup:
It may not be ideal to use these as a combination in this setting until further investigation into a larger cohort of patients
Optimizing Oral Chemotherap:
Intravenous (IV) taxane therapy, including with paclitaxel:
Is highly effective in high-risk breast cancer
To date, oral paclitaxel in combination with other treatments, such as immunotherapy:
Has yet to demonstrate similar benefits as the IV formulation but could represent a desirable treatment option that allows patients to use at-home administration and avoid needle sticks:
There are also some favorable side-effect profiles of oral paclitaxel compared to IV paclitaxel:
Less peripheral neuropathy and alopecia:
Which can impact quality of life
Findings from a recent phase 3, head-to-head comparison of oral paclitaxel with IV paclitaxel have opened the door to new questions about whether an oral formulation can be optimized in combination with other treatments:
In that study, investigators observed a higher confirmed tumor response with oral paclitaxel and a numerically (although not statistically) higher progression-free and overall survival than with IV paclitaxel
In the phase 3 trial that compared oral paclitaxel to IV paclitaxel:
The overall risk–benefit ratio of oral paclitaxel over IV paclitaxel was questionable:
The U.S. Food and Drug Administration [FDA] did not approve oral paclitaxel due to concerns regarding 19-week objective response rate per blinded independent central review, where a reread of data may have brought on unmeasured bias
In addition, FDA cited febrile neutropenia as a safety concern
In the I-SPY2 study, compared with IV paclitaxel:
Oral paclitaxel caused less peripheral neuropathy;
But led to increased rates of nausea, diarrhea, neutropenia, anemia, and urinary tract infections
In an effort to identify optimal treatment options, the ongoing I-SPY2 trial is investigating the efficacy of several experimental therapies for early-stage breast cancer with a high risk of recurrence, including a combination treatment featuring oral paclitaxel
Multiple investigational arms are assessed in parallel, using neoadjuvant chemotherapy plus an investigational drug (the treatment arm) versus neoadjuvant chemotherapy alone (the control arm):
The primary endpoint is pCR
Biomarker assessments performed at baseline are used to classify patients into 1 of 10 predefined signature subtypes:
Based on hormone receptor (HR), erbB-2 receptor, and MammaPrint status
Adaptative randomization in I-SPY2 preferentially assigns patients to new or standard regimens based on Bayesian predictive probabilities of rates of pCR for each subtype
Regimens that demonstrate a high predictive probability of being statistically superior to standard treatment in at least 1 of 10 predefined signatures in a hypothetical phase 3 confirmatory trial “graduate” from the study
In the analysis women with early-stage breast cancer:
Considered high risk based on HR, erbB-2 receptor, and MammaPrint status were randomly assigned to the control group or experimental treatment
The experimental arm received oral paclitaxel plus encequidar (which is required for the body to absorb oral paclitaxel) followed by carboplatin and dostarlimab and then chemotherapy with doxorubicin / cyclophosphamide
The control arm received paclitaxel plus doxorubicin /cyclophosphamide
Patients with HER2-positive disease also received trastuzumab during the first 12 weeks of the study
In the 106 randomly assigned patients, 44 had HR-positive/HER2-negative disease, 56 had triple-negative breast cancer, and 6 had HER2-positive breast cancer
Among the 10 predefined biomarker signatures in which the treatment regimen was assessed, it was most successful in the triple-negative signature:
In this group, the treatment had a predicted pCR of 48% versus 29% in the control arm, causing the experimental treatment to “graduate” from the study:
This is the first study to combine an oral taxane with an immune checkpoint inhibitor
It demonstrated that the combination of oral chemotherapy and dostarlimab is safe and feasible
The combination of chemotherapy and dostarlimab can be potentially effective in triple-negative breast cancer
The effectiveness of oral paclitaxel plus encequidar was comparable to that of IV paclitaxel and with lower rates of neuropathy and alopecia than with the IV treatment:
Suggesting this oral agent may be an attractive alternative to IV paclitaxel to be used as single agent
Several phase 3 trials were conducted between 2015 and 2017:
Which directly compared taxane-based induction chemotherapy (IC) with concurrent chemoradiation (CCRT):
On groups of unselected locally advanced head and neck cancer (LAHNC):
Most of IC protocols were followed by CCRT:
But one trial had RT combined by targeted therapy
The first of this list includes the multi-center PARADIGM trial:
That considered high-risk patients with high nodal load
A hundred and forty-five patients were randomized to either be treated with CCRT with 2 cycles of 100 mg/m2 cisplatin or 3 cycles of TPF followed by CCRT with weekly carboplatin for good responders or weekly docetaxel for the rest
No significant differences in progression free survival (PFS) or overall survival (OS) were detected between groups
Unexpectedly, both groups were advantaged with good survival results:
3 year overall survival (OS) 73% (95% CI 60–86) in IC, vs. 78% (66−86) in CCRT (Haddad et al., 2013)
A second trial, DeCide:
Used CCRT in both arms with 2 cycles of induction with TPF in the experimental arm
Here, 285 patients were recruited and randomized
Cancer deaths and distant metastases were reduced with induction:
But serious adverse events and non-cancer related deaths increased
As well, none of the survival measures improved with IC
Similar to the PARADIGM trial:
Mean OS was higher than predicted in both groups, and patients were prescribed with an unconventional regimen (including fluorouracil, docetaxel, and hydroxyurea)
Moreover, both mentioned trials were disadvantaged for being underpowered:
200 were planned for PARADIGM and 400 for DeCide (Cohen et al., 2014)
The 3-armed Spanish TTCC trial:
Was the first well-designed study to compare:
TPF-CCRT, PF-CCRT, and CCRT, with standard high-dose cisplatin combined with RT
The trial reached its accrual goals and 439 patients were analyzed
The results did show a trend of higher PFS, in favor of induction over CCRT:
But only as a result of per-protocol analysis:
In fact 27% of patients in the TPF arm did not receive the treatment as scheduled:
Likewise, intention to treat analysis showed no PFS advantage in any group (logrank P = 0.56) (Hitt et al., 2014)
Moreover, in a follow-up study, OS, PFS, and TTF were neither significantly different when intention to treat analysis compared TPF followed by CCRT with CCRT alone (Hitt et al., 2021 Apr)
The GORTEC 2007–02 trial:
Examined TPF induction followed by cetuximab with RT in comparison to CCRT with 3 cycles of carboplatin and fluorouracil on 370 LAHNC patients
Similar to DeCide, there was a decrease in distant metastases in the TPF arm:
Though the documented response rate was poor (45%), and both PFS and OS were almost identical in the two groups
Nevertheless, the concerning effect was that the rate of early deaths was as high as 6.6% (Geoffrois et al., 2016)
The Italian GSTTC:
A primarily phase 2 (and 3) study with a 2 × 2 factorial design:
Evaluated CCRT with cisplatin (cumulative dose of 160 mg/m2) and 5-FU (800 mg/m2/ 96 h) or cetuximab with or without a modified TPF (docetaxel 75 and cisplatin 80 mg/m2 day 1 and 5-fluorouracil 800 mg/m2/day 96-h) induction
Among 414 patents over half were oropharyngeal cases, and most patients had excellent performances (79% ECOG 0 and the rest 1)
Outcomes were far better with IC with a median OS of 54.7 vs. 31.7 months in favor of IC and a significantly higher PFS (median 29.7 months vs. 18.5, HR 0.72; 95% CI 0.56–0.93; p = 0.013) and OS (HR 0.74; 95% CI 0.56–0.97; p = 0.031)
The results of TPF followed by CCRT versus CCRT alone:
Was not significantly different:
While the comparison of TPF followed by cetuximab and RT showed to be superior to cetuximab and RT alone
Furthermore, compliance with IC was high, as 93% of patients were able to receive the planned 3 cycles of TPF, and early deaths were 1%
This was a unique trial that showed OS benefit for IC but likely because of the good prognose of the subjects
Is a clinical diagnosis defined by the American Joint Committee on Cancer as a:
Diffuse erythema and edema involving approximately a third or more of the skin of the breast:
It is staged cT4d
A punch biopsy of the skin:
Demonstrates tumor emboli within dermal lymphatics:
Approximately 75% of the time
A negative skin biopsy does NOT preclude the diagnosis:
As it is clinical
The appearance may lead to misdiagnosis of mastitis or breast cellulitis
The rapid evolution of symptoms (within 3 to 6 months):
Distinguishes IBC from a locally advanced breast cancer with associated edema
IBC is rare:
Present in 2% to 4% of breast cancer patients:
Although the reported annual incidence has been increasing
The tumor biology is disproportionately ER negative and HER2 amplified, compared with non-IBC
Patients should be evaluated in a multidisciplinary setting for trimodal therapy:
Treatment should be initiated with neoadjuvant chemotherapy:
Followed by aggressive local therapy
The majority of patients with IBC:
Present with clinical lymph node involvement
Sentinel lymph node biopsy is not reliable in IBC:
Due to blockage of dermal lymphatics:
Thus axillary dissection should be performed
Following neoadjuvant chemotherapy:
Modified radical mastectomy is the appropriate surgery:
Skin should not be spared:
So as not to leave behind residual disease:
Immediate reconstruction should be avoided
Patients should receive post-mastectomy radiation to the skin, chest wall, and regional lymph nodes following surgery to optimize local control
Survival in IBC has improved with trimodal therapy:
A recent analysis of Surveillance, Epidemiology, and End Results data:
Evaluated 10,197 patients with non-metastatic IBC between 1998 and 2010
Patients who underwent trimodal therapy had improved 5- and 10-year survival:
55.4% and 37.3% over those that did not receive all 3 modalities
Survival was lowest at 10 years (16.5%) for patients who underwent surgery alone
References
Amin MB, Edge S, Greene F, et al., eds. AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer; 2017
Hance KW, Anderson WF, Devesa SS, Young HA, Levine PH. Trends in inflammatory breast carcinoma incidence and survival: the surveillance, epidemiology, and end results program at the National Cancer Institute. J Natl Cancer Inst 2005;97(13):966-975.
Menta A, Fouad TM, Lucci A, et al. Inflammatory breast cancer: what to know about this unique, aggressive breast cancer. Surg Clin North Am. 2018;98(4):787-800.
Rueth NM, Lin HY, Bedrosian I, et al: Underuse of trimodality treatment affects survival for patients with inflammatory breast cancer: an analysis of treatment and survival trends from the National Cancer Database. J Clin Oncol. 2014;32(19):2018-2024.
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.
Rodrigo Arrangoiz MS, MD, FACS, FSSO 