- Basic principles of systemic adjuvant therapy:
- Are shared between all breast cancer types and are largely influenced by tumor biology rather than histology
- Generally, hormone receptor–positive
cancers should receive endocrine therapy:- Applicable to the majority of ILCs
- Chemotherapy is typically offered for locally advanced cancers and for early-stage cancers with high-risk features such as:
- High grade
- Large size
- Involved lymph nodes
- High 21-gene recurrence scores
- Patients with HER-2+ tumors measuring greater than 1 cm:
- Should receive additional anti-HER-2 targeted therapy as well
- Whereas those with triple negative tumors:
- Are generally offered chemotherapy for tumors
greater than 0.5 cm
- Are generally offered chemotherapy for tumors
- Contemporary systemic therapies have been shown to have a significant impact on:
- Locoregional and distant disease control as well as overall survival
- Tumor biology:
- Is key in the selection and efficacy of adjuvant therapies
- Most relevant to ILC, with a typically high ER content, are low rates of local recurrence (approximating 3%):
- Reported among women with ER-positive tumors who receive endocrine therapy in the modern era
- Studies comparing the impact of systemic hormonal and chemotherapy in ILC and IDC are summarized here [Table]
- Importantly, these studies contain a mix of ER-positive and ER-negative patients, and hormone receptor status is apparent as a central determinant of response
- Interestingly, studies of the utility of Oncotype Dx in ILC:
- Have shown that ILCs rarely (less than 2%) have a high recurrence score compared with rates approximating 20% in IDCs
- Support for adjuvant endocrine therapy:
- Comes from a number of trials demonstrating a
significant reduction in risk of recurrence at 15 years:- As summarized in a large Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) meta-analysis
- Although large studies specific to ILC
patients remain limited, some data suggest a greater benefit with aromatase inhibitors compared with tamoxifen:- In a retrospective analysis of the prospective BIG 1-98 trial, a larger magnitude of
benefit was observed with adjuvant letrozole than with tamoxifen in the ILC subset:- With disease-free survival rates of 82% with letrozole versus 66% with tamoxifen at the 8-year follow-up, and overall survival rates of 89% with letrozole versus 74% with tamoxifen
- This differential response in favor of aromatase inhibitors may be attributed to:
- A paradoxical de novo resistance to tamoxifen and resultant proliferative response, which has been observed in an in vitro study of lobular carcinoma cell lines
- However, the Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial:
- Which randomized patients to exemestane alone, or an “early switch” from tamoxifen for a total of 5 years of therapy, showed similar efficacy of both regimens for IDC and ILC
- There was evidence of an impact of ER content, with suggested benefit from monotherapy for ER-rich patients (quantified by Allred score) compared with a benefit from sequential treatment strategy for
ER-poor patients, regardless of histology
- In a retrospective analysis of the prospective BIG 1-98 trial, a larger magnitude of
- Comes from a number of trials demonstrating a
- There have not yet been any large randomized trials examining the impact of adjuvant chemotherapy regimens specifically for ILC:
- Although retrospective analyses do not suggest any overwhelming reasons to deny adjuvant chemotherapy to patients with ILC who otherwise have indications for treatment, the poor response of ILCs to chemotherapy in the neoadjuvant setting:
- Suggests a lower chemosensitivity of these cancers
- Although retrospective analyses do not suggest any overwhelming reasons to deny adjuvant chemotherapy to patients with ILC who otherwise have indications for treatment, the poor response of ILCs to chemotherapy in the neoadjuvant setting:
- In a retrospective study including 3,685 ILCs
and 19,609 IDCs, divided into groups treated either by adjuvant hormonal treatment alone or
hormonal and chemotherapy:- For the ILC subset, 10-year survival rates were 68% after hormonal treatment alone and 66% with combination therapy (p = .45), suggesting that chemotherapy had limited benefit in postmenopausal patients with lobular cancers already receiving hormonal therapy:
- However, chemotherapy may hold much greater value for the small minority of ILCs
with ER– or HER-2+ receptor status
- However, chemotherapy may hold much greater value for the small minority of ILCs
- For the ILC subset, 10-year survival rates were 68% after hormonal treatment alone and 66% with combination therapy (p = .45), suggesting that chemotherapy had limited benefit in postmenopausal patients with lobular cancers already receiving hormonal therapy:
- In a retrospective subset analysis of the prospective phase III Herceptin Adjuvant (HERA) trial of patients with HER-2+ tumors:
- There was a similar magnitude of benefit observed with 1 year of adjuvant trastuzumab among those with ILC and IDC (disease-free survival HR 0.63 versus 0.77, p = .49) at a median 4 years of follow-up
- Presently, standard treatment with adjuvant trastuzumab is recommended for HER-2+ ILCs
Rodrigo Arrangoiz MS, MD, FACS, FSSO 