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Masteronderzoek Interne Oncologie

Comparison of recurrence-free survival, breast cancer-specific survival and overall survival between invasive lobular breast carcinoma and invasive breast carcinoma of no special type

Background

Invasive lobular carcinoma (ILC) of the breast is the second most common subtype of breast cancer after invasive breast carcinoma of no special type (NST), accounting for up to 15% of all breast cancer cases. ILC and NST subtypes clearly differ from each other. Compared to NSTs, ILCs are relatively often not palpable and not visible by mammography, and more often multifocal, multicentric and bilateral. Further, they show more often expression of estrogen receptor (ER) and progesterone receptor (PR), but no amplification of human epidermal growth factor receptor 2 (HER2), and a lack of E-cadherine expression.

Problem description

Despite the clear histological and molecular differences, in clinical practice no distinction between ILC and NST subtypes is made regarding treatment with chemotherapy. Clinical outcomes, however, differ significantly between both subtypes: pathological complete response rates on neoadjuvant chemotherapy were shown to be lower for patients with ILC (<5%) than for NST patients (~25%). Furthermore, for ILC patients less down staging and less breast conserving surgery was observed after neoadjuvant chemotherapy. This suggests that ILC may be less sensitive to chemotherapy than NST. Although the vast majority (>90%) of the ILCs are ER-positive and HER2-negative (ER+/HER2-) – a phenotype known to be less sensitive for chemotherapy – previous analyses on the response on chemotherapy in ILC and NST seldom took into account hormone receptor status and HER2 status. Importantly, studies comparing long-term outcomes of chemotherapy between ILC patients and NST patients are scarce and showed inconclusive results. In view of the adverse effects of chemotherapy, an important question is whether ER+/HER2- ILC patients do experience less benefit on the long term from chemotherapy than ER+/HER2- NST patients. If confirmed, a burning follow-up question from the patient perspective is which ILC patients should and should not be treated with chemotherapy.

Solution/research direction

To identify predictors of chemotherapy benefit in ER+/HER2- ILC patients thereby preventing unnecessary side effects in those for whom chemotherapy does not improve outcome.

Purpose of the current study

To eventually reach the envisioned solution, we will first compare the effect of chemotherapy on recurrence-free survival, breast cancer-specific survival, and overall survival between ER+/HER2- ILC and NST patients.

Type of research

For this retrospective cohort study you will:
select female patients who are diagnosed with ER+/HER2- ILC or NST from our hospital-based breast cancer database,
collect additional data on date and site of recurrent disease, cause of death, timing of systemic treatment from the institutional and regional (if necessary) patient hospital files,

compare the above described endpoints among ILC patients and NST patients treated with endocrine therapy as well as chemotherapy,
perform statistical analyses, and interpret the results, discuss the final results in an oral presentation, and write them down in a scientific report.

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