Invasive lobular carcinoma: response to neoadjuvant letrozole therapy

Abstract

Invasive lobular cancer (ILC) responds poorly to neoadjuvant chemotherapy but appears to respond well to endocrine therapy. We examined the effectiveness of neoadjuvant letrozole in postmenopausal women (PMW) with estrogen receptor (ER)-rich ILC. PMW were considered for treatment with neoadjuvant letrozole if they had ER-rich, large operable, or locally advanced cancers, or were unfit for surgical therapy. Tumor volume was estimated at diagnosis and at 3 months using calipers (clinical), ultrasound, and mammography. At 3 months, if physically fit, women were assessed for surgery. Responsive women with cancers too large for breast-conserving surgery continued with letrozole. Patients had surgery or were switched to alternative therapy if tumor volume was increasing. Sixty-one patients (mean age, 76.2 years) with 63 ILCs were treated with letrozole for ≥ 3 months. The mean reduction in tumor volume at 3 months was 66% (median, 76%) measured clinically, 61% (median, 73%) measured by ultrasound, and 54% (median, 60%) measured by mammography. Surgery was possible at 3 months in 24 cancers in 24 patients, and all but two of the remaining patients continued with letrozole therapy for a median duration of 9 months. At the time of this publication, 40 patients with a total of 41 cancers have undergone surgery. The rate of successful breast conservation was 81% (25/31). Twenty-one patients have continued with letrozole monotherapy, and 19 remain controlled on letrozole at a median of 2.8 years. There is a high rate of response to letrozole in PMW with ER-rich ILC.

Telomere length alterations unique to invasive lobular carcinoma

“…ILC differs biologically and clinically from invasive ductal carcinoma (IDC). ILC occurs more often in older women, has increased incidence secondary to hormonal replacement therapy, tends to maintain hormone receptor signaling via estrogen receptor (ER) and progesterone receptor (PR), is often associated with lobular carcinoma in situ (LCIS), responds poorly to neoadjuvant chemotherapy, and metastasizes to unusual sites including the gynecologic and gastrointestinal tracts [4][5][6][7][8].…”

Molecular Changes in Lobular Breast Cancers in Response to Endocrine Therapy

“…Inactivation of E-cadherin (CDH1) by a variety of molecular mechanisms is considered a defining characteristic of ILC. When compared with the more common invasive breast cancers of no special type, also known as invasive ductal carcinomas (IDC), ILC is more likely to be estrogen receptor-positive (ER þ ) and of lower nuclear grade (3). ILC is often large at diagnosis and there have been numerous reports on the response to neoadjuvant chemotherapy.…”

“…It was thought that patients with ILC are significantly less likely to have a pathologic complete response than patients with IDC; however, a recent study concluded that ILC represents a heterogeneous group of tumors and the difference in response to neoadjuvant chemotherapy is largely explained by differences in molecular characteristics, particularly hormone receptor and HER2, and is independent of lobular histology (4). ILC have been shown to respond well to endocrine therapy (2) and we recently described the clinical response to neoadjuvant letrozole in a series of 61 patients (3). The lack of understanding of how lobular breast cancer responds to treatment is compounded by the paucity of research models (reviewed in ref.…”

Issues Affecting the Loco-regional and Systemic Management of Patients with Invasive Lobular Carcinoma of the Breast

“…Given the lower rates of pCR and high rates of ER positivity, some authors specifically suggest not to give chemotherapy for classic ILC, but instead to limit systemic treatment to endocrine manipulation in the neo‐adjuvant and adjuvant settings . In support of this, high rates of responsiveness to neo‐adjuvant letrozole therapy have been demonstrated . In a series of 61 postmenopausal patients with estrogen receptor positive ILC that were not eligible for BCS or who were deemed unfit for surgery, neo‐adjuvant letrozole therapy allowed for a clinical response or stable disease in 95% of the patients at 3 months.…”