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
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
In 2022, both the US Food and Drug Administration and the European Union approved adjuvant olaparib, a PARP inhibitor, for the treatment of patients with deleterious or suspected deleterious germline BRCA mutation (gBRCAm) and a diagnosis of HER2-negative, high-risk, early-stage breast cancer treated with neoadjuvant or adjuvant chemotherapy
A diagnostic companion test for germline BRCA status is needed to select patients for this treatment
Olaparib was approved on the basis of findings of the OlympiA trial, a phase 3 trial in which patients carrying a germline BRCA alteration and a diagnosis of HER2-negative, high-risk, early-stage breast cancer were randomly assigned to receive 1 year of olaparib or placebo after (neo)adjuvant chemotherapy
A statistically significant improvement in invasive disease-free survival and overall survival was demonstrated in patients in the olaparib arm compared with the placebo arm
The safety profile of olaparib was consistent with previously reported side effects
As with other early breast cancers (eg, hormone-positive or triple-negative), risk for recurrence of a HER2-positive tumor is generally dependent on tumor size, presence of positive axillary lymph nodes, tumor grade, and other histologic and patient factors
Before the development of effective anti-HER2 therapies, such as trastuzumab, novel anti-HER2 tyrosine kinase inhibitors (TKIs), or antibody drug conjugates (ADCs) HER2 positivity was associated with poor prognosis
The degree of HER2 positivity (ie, IHC 2+/FISH amplified vs IHC 3+) is not correlated with recurrence risk, although it may be associated with greater responsiveness to anti-HER2–targeted therapies
Patients with early-stage, HER2-positive tumors with clinically positive lymph nodes are candidates for neoadjuvant systemic treatment with chemotherapy and pertuzumab plus trastuzumab
According to the American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO), decisions about adding chemotherapy to adjuvant endocrine therapy are individualized on the basis of patient and disease factors, including results of genomic assays
Most cases of small ER-positive, PR-positive, HER2-negative, node-negative breast cancer have a good prognosis with endocrine therapy alone and do not require adjuvant chemotherapy
By contrast, tumors that are high-grade, with higher measures of proliferation and lower levels of ER/PR expression, tend to be less sensitive to endocrine treatment and are more likely to benefit from adjuvant chemotherapy
Although assessment of response to neoadjuvant endocrine therapy or chemotherapy is used in the setting of locally advanced breast cancer, particularly when the size and/or location of the tumor preclude breast-conserving surgery, patients with very small, early, HER2-negative, hormone-positive cancers are generally treated with surgery first, followed by radiation therapy and consideration of adjuvant therapy with an endocrine regimen, chemotherapy, or both
Ki67 is an indirect measure of cell proliferation
Although a high Ki67 score is often considered a marker for poorer prognosis in early breast cancer, it cannot predict the benefit of chemotherapy as a single measure
Recently, the International Ki67 in Breast Cancer Working Group concluded that Ki67 has limited value for treatment decisions due to questionable analytical limitations
Inflammatory breast cancer is an aggressive type of breast cancer that requires urgent workup and treatment
Detection by mammography is limited due to low sensitivity; hence, diagnosis of inflammatory breast cancer is based on clinical factors and defined as a rapid onset of breast erythema, edema and/or peau d’orange, and/or warm breast, with or without an underlying palpable mass
Immediate referral to medical and surgical oncologists is essential when inflammatory breast cancer is suspected
Because it is not uncommon for women with inflammatory breast cancer to have metastatic disease at the time of diagnosis, inflammatory breast cancer should be staged with full-body imaging, such as PET-CT or CT of the chest, abdomen, and pelvis, plus a bone scan
When the presence of metastatic disease is ruled out, inflammatory breast cancer is treated with chemotherapy upfront (ie, neoadjuvant), before surgery
Axillary adenopathy may or may not be present
Crusting and retraction of nipples may or may not occur
Rodrigo Arrangoiz MS, MD, FACS, FSSO 