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Cancer Drug Resist 2018;1:266-302 I http://dx.doi.org/10.20517/cdr.2018.18 Page 301

Aim: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is associated with
poor prognosis. Due to the lack of hormone sensitivity and the significant heterogeneity amongst triple
negative breast cancer there are no approved targeted therapies and cytotoxic chemotherapy remains as
the standard treatment. Although response rates to chemotherapy in early disease are high, patients with
TNBC remain at high risk of relapse and prognosis remains poor in comparison to other types of breast
cancer. There is currently lack of data on this subpopulation of patients with regards to the resistance to
chemotherapy used for early disease (primary resistance) and advanced disease (secondary resistance)
through patients’ clinical treatment pathway.

Methods: Data were collected retrospectively from 163 patients diagnosed with triple negative cancer in
Maidstone and Tunbridge Wells Hospitals between 2011-2017. Clinico-pathological characteristics and pa-
tient treatment outcomes were obtained by accessing electronic records.

Results: One hundred and sixty-three patients with TNBC were identified with a median age of 57. Of the
patients who received treatment for early disease, 50 % of the relapses occurred within 12 months of this
treatment (i.e., primary resistance). 33 patients had metastatic disease, 13 of whom received 1st line pallia-
tive chemotherapy. Over 50% (6) of patients experienced disease progression in less than 3 months from
commencing treatment (often termed secondary resistance). Patients who subsequently received 2nd and
3rd line chemotherapy experienced disease progression in less than 1.5 month.

Conclusion: Rates of disease recurrence are consistent with the literature and early progression on treat-
ments exemplifies the inherent chemo-resistance with this phenotype. Continued basic scientific investiga-
tion is needed to examine resistance and develop targeted treatments for this poor prognosis disease.

64. Investigating resistance mechanisms to tamoxifen in oestrogen-receptor positive breast
cancer

2
1
Joanna L. Bird , Jindrich Cinatl , Mark Wass , Martin Michaelis 1
1
1 University of Kent, School of Biosciences. Canterbury, Kent, UK
2 Institute of Medical Virology, Clinics of the Goethe-University, Frankfurt am Main, Germany

Tamoxifen is the most commonly used adjuvant therapy used to treat oestrogen receptor (ER) positive
breast cancer. However, development of resistance to this drug during treatment regimens presents a se-
rious clinical problem. Over the last 20 years, many advances have been made into understanding the
mechanisms of oestrogen signalling in cancer, and the biology of oestrogen receptors, which helps us pre-
dict how resistance to this drug arises. However, not everything is understood about the mode of action of
tamoxifen as it is known to have both agonistic and antagonistic properties dependent on tissue type. In
recent years, it has been increasingly reported that tamoxifen does not just target ERs, although the vast
majority of its actions are still considered to be facilitated by these receptors. It is thought to also elicit non-
specific actions in vivo, which ultimately alters the scientific community’s perspective of this familiar drug.
This study introduces a new panel of tamoxifen resistant ER+ breast cancer cell lines. The cell lines have
been characterised for ER expression, response to endogenous oestrogen, and sensitivity to a range of anti-
cancer agents.

65. The efficacy of doxorubicin-loaded nanoparticles in drug-resistant cancer cell lines

2
3
1
1
Hannah Onafuye , Stefan Pieper , Jindrich Cinatl Jr , Mark N. Wass , Martin Michaelis 1
1 University of Kent, School of Biosciences, Canterbury, Kent, UK
2 Institute of Pharmaceutical Technology and Biopharmacy, University of Münster, Münster, Germany