triple - negative breast cancer ( tnbc ) accounts for approximately 15% of all breast tumors [ 1 , 2 , 3 ] .
it is characterized by a lack of expression of the estrogen receptor , progesterone receptor , and human epidermal growth factor receptor 2 ( her2 ) [ 1 , 3 ] . due to the absence of expression of these receptors ,
targeted regimens using hormonal or anti - her2 therapy are ineffective , and treatment options are generally restricted to systemic chemotherapies . despite initial responses to standard cytotoxic therapies , relapse is common , and tnbc is associated with an aggressive clinical course .
this is reflected by a high rate of visceral metastases , notably including the brain , rapid progression on systemic treatment , and poor survival times [ 1 , 2 , 3 ] .
substantial overlap exists between brca1-positive breast cancer and tnbc , in terms of a number of shared clinical and pathological features ; in addition , both frequently exhibit high histologic grade tumors and aggressive courses .
although not all patients with tnbc exhibit brca1 mutations , a considerable proportion of brca1 carriers do develop this condition . there is an urgent need for new treatment options in tnbc , particularly for those patients who are also brca1 positive . in the us ,
no targeted therapies are currently approved for women with tnbc , and cytotoxic chemotherapy remains the standard of care for such patients , including those with brca1 mutations .
the angiogenesis inhibitor bevacizumab is one of a number of targeted therapies currently being evaluated in clinical trials .
promising results with bevacizumab plus chemotherapy have been reported in patients with tnbc being treated in neoadjuvant , first- , and second - line settings [ 4 , 5 , 6 , 7 ] ; however , no benefit has yet been demonstrated in the adjuvant setting .
recently , a novel regimen of bevacizumab combined with carboplatin , as well as nanoparticle albumin - bound paclitaxel particles ( nab - paclitaxel ) , has produced high response rates in phase ii trials of patients with tnbc in neoadjuvant   and first - line settings . while the individual contribution of each of the experimental agents in these trials is difficult to determine
, the studies suggest that carboplatin plus nab - paclitaxel may be an active cytotoxic combination in patients with tnbc .
the case study reported here describes a patient with previously treated triple - negative brca1-positive breast cancer , who showed a strong response to nab - paclitaxel , first in combination with carboplatin and subsequently as monotherapy , after presenting to the author 's clinic with severe metastatic disease .
a 51-year - old caucasian woman was admitted with significant abdominal pain in june 2012 .
the patient had been diagnosed with cancer of the left breast at a private clinic in april 2008 , and the tumor was initially thought to be a small - cell carcinoma . following the initial diagnosis , the patient was treated with 4 cycles of carboplatin and etoposide ( vp-16 ) ; unfortunately , dosing information is not available for either drug .
this regimen was completed by september 2008 and , at that time , the patient had not received any radiation or systemic therapy other than the initial treatment of carboplatin plus etoposide .
the patient 's response to this regimen was excellent , with complete regression of the disease .
following completion of the initial treatment , a review of the pathology findings established that the tumor was consistent with infiltrating ductal carcinoma , and that it was triple negative .
routine follow - up appointments took place , and , in november 2009 , the patient was diagnosed with a recurrent infiltrating carcinoma of the left breast at the same clinic that had initially diagnosed and treated her .
pathology tests performed at this time revealed a grade iii , 2.5-cm carcinoma , although neither of the 2 sentinel lymph nodes showed involvement .
in addition , the patient 's brca1 status was tested , and she was identified as a mutation carrier .
treatment for the carcinoma recurrence took place at loyola university , chicago , from march to july 2010 .
the patient received neoadjuvant dose - dense doxorubicin at 60 mg / m plus cyclophosphamide at 600 mg / m once every 2 weeks for 4 cycles .
in addition , pegfilgrastim was administered at a dose of 6 mg on the second day of each cycle to stimulate neutrophil production . as there was no evidence of metastasis , this regimen
the patient continued to be actively monitored and , in march 2012 , she presented with expressive aphasia . upon further investigation ,
diffuse brain metastases were discovered , and treatment commenced with whole - brain radiation therapy ( 30 gy in 10 fractions ) at loyola university .
this resulted in a significant improvement of the patient 's symptoms and regression of the brain metastases .
follow - up continued at loyola university until june 2012 when , during a routine clinic visit , the patient experienced severe abdominal pain and was admitted to the author 's clinic .
a ct scan of the abdomen and pelvis performed on the day of admission revealed a large mixed cystic and solid mass in the region of the porta hepatis , posterior to the uncinate process of the pancreas .
this scan also revealed worrying signs of metastasis , namely necrotic adenopathy ; celiac , retroperitoneal , and left iliac chain adenopathy ; multiple tiny hypodensities in the liver , and right renal nodules of abnormal appearance .
the following day , a separate ct scan of the chest found more than 20 diffuse , bilateral , pulmonary metastases .
figure 1 shows abdominal and chest ct scans of the patient taken prior to treatment .
urgent radiation therapy to the abdomen commenced that day , as the patient had reported a maximum score of 10 on a rating scale for her abdominal pain .
in view of the patient 's history , the underlying cause was suspected to be metastatic breast cancer .
a biopsy of the left lung mass was performed on the third day of admission , and a general pathologist identified non - small cell carcinoma . after discussing the pathology findings , it was agreed that the cancer was very poorly differentiated and high grade , and , although it was likely to be of lung origin , it was difficult to exclude other cancers , including malignancies of the breast or abdomen .
the patient elected to continue treatment at the author 's clinic and , on june 12 , 2012 , she started a carboplatin plus nab - paclitaxel regimen .
the dosing schedule was carboplatin 450 mg ( area under the curve = 5 ) once every 3 weeks , plus nab - paclitaxel at 100 mg / m once a week for 3 weeks in a 4-week cycle . despite filgrastim injections to stimulate neutrophil production ,
carboplatin was removed from the regimen after 4 cycles of treatment due to the persistent occurrence of neutropenia , which resulted in frequent dose delays ( see table 1 ) .
however , from the end of august 2012 , the dose was reduced to 90 mg / m once a week for 3 weeks in a 4-week cycle , due to a decrease in body weight , body mass index , and body surface area .
whole - body ct scans , including brain imaging , were scheduled to be performed on a regular basis , along with assessments of bone scans , laboratory results , and tumor markers . in this regard , a whole - body ct scan performed in october 2012 revealed that the patient had responded significantly to the therapy , as evidenced by a reduction of at least 50% in bulky tumor burden .
the patient also reported decreased abdominal pain and shortness of breath . the positive response to nab - paclitaxel
the number of metastases in the lung appeared to have reduced to 1 , and the large abdominal mass had decreased in size .
figure 2 shows abdominal and chest ct scans taken after treatment with nab - paclitaxel . at follow - up in march 2013 ,
the patient was continuing to receive nab - paclitaxel and confirmed that the treatment had been well tolerated , with no treatment - related adverse events .
this contrasted significantly with her original presentation to the author 's clinic , when she was bedridden with severe disease and related symptoms .
a brain mri scan carried out on april 18 , 2013 , as part of routine tumor surveillance , revealed a recurrence of the brain metastases .
however , whole - body ct scans carried out 5 days later confirmed that the patient 's response to nab - paclitaxel was still being maintained in all areas other than the cns .
on april 24 , treatment was initiated with temozolomide 100 mg / m daily on days 17 and 1521 of each 28-day cycle , plus irinotecan administered at a dose of 125 mg / m once every 2 weeks .
unfortunately , the patient 's condition deteriorated and she died on july 2 , 2013 .
it is well established that tnbc is associated with a particularly aggressive clinical course [ 1 , 3 ] .
therapeutic options are limited , and standard cytotoxic chemotherapy remains the mainstay of treatment , despite the disease progressing quickly in the majority of women [ 1 , 2 , 3 ] .
median survival times of around 1 year have been reported along with a median duration of response to first - line therapy of just 12 weeks .
there is an urgent need for the development of novel treatment strategies that will significantly increase survival times .
nab - paclitaxel is an albumin - bound form of paclitaxel with a mean particle size of approximately 130 nm .
it is able to target delivery of paclitaxel to tumors by interacting with albumin receptors involved in drug transport .
nab - paclitaxel displays an improved therapeutic index compared with standard solvent - based paclitaxel , allowing the safe infusion of higher doses in a shorter time span with no requirement for premedication .
nab - paclitaxel is currently approved for the treatment of breast cancer after either failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy .
recent reports have shown the potential for nab - paclitaxel to be used in the treatment of tnbc .
for example , a japanese case study reported a complete response in a patient with tnbc and lymph node metastases who received 8 cycles of adjuvant nab - paclitaxel therapy following surgery .
however , the majority of ongoing research with nab - paclitaxel in tnbc is in combination with bevacizumab , which itself has provided modest improvements in efficacy versus chemotherapy alone in neoadjuvant , first- , and second - line settings [ 4 , 5 , 6 , 7 ] .
two phase ii studies have recently reported promising activity with the combination of nab - paclitaxel , bevacizumab , and carboplatin in first - line   and neoadjuvant   treatment of patients with tnbc , and the combination was deemed to be well tolerated .
another phase ii study examined the efficacy and safety of nab - paclitaxel administered in combination with bevacizumab and gemcitabine as first - line treatment for her2-negative , metastatic breast cancer .
a subset of 13 patients was identified as having tnbc , and this cohort demonstrated a clinical benefit rate  defined as complete response , partial response , or stable disease  of 85% .
a case study has been published of one of the tnbc participants in this trial , who achieved long - term complete remission of almost 2 years and a progression - free survival of just over 2.5 years . as a consequence of these findings , the phase ii / iii tnacity trial ( www.clinicaltrials.gov nct01881230 )
will compare nab - paclitaxel plus gemcitabine with nab - paclitaxel plus carboplatin , and also with gemcitabine plus carboplatin , with the aim of clarifying how to best use existing drugs in patients with tnbc .
the case study described in this paper adds to previous trials and reports indicating the potential efficacy of nab - paclitaxel in tnbc , either as monotherapy in a later - line setting , or in combination with bevacizumab and chemotherapy agents at an earlier stage . to the author 's knowledge , this is the first account of a patient with metastatic , triple - negative , brca1-positive breast cancer achieving a strong response to treatment with nab - paclitaxel , which was sustained from the first routine whole - body ct scan in october 2012 until the recurrence of brain metastases in april 2013 .
this case study also suggests that nab - paclitaxel is well tolerated , adding to the argument in favor of further investigations of this agent in metastatic tnbc , particularly in patients who are also brca1 positive .
 our case describes a 51-year - old female , diagnosed in april 2008 with a triple - negative , brca1-positive , infiltrating ductal carcinoma of the left breast . 
 initial platinum - based therapy resulted in a complete regression until november 2009 , when a recurrence of the disease was detected . 
 as no evidence of metastasis was found , a dose - dense regimen of doxorubicin plus cyclophosphamide was administered , followed by paclitaxel . 
 the patient was actively monitored until march 2012 , when brain metastases were discovered and successfully treated with whole - brain radiation therapy . 
 three months later , the patient experienced severe abdominal pain , and ct scans revealed extensive metastatic disease , including a large mass in the abdomen and more than 20 bilateral pulmonary metastases . 
 treatment commenced with carboplatin plus nab - paclitaxel . 
 however , carboplatin was stopped after 4 cycles due to persistent neutropenia , and nab - paclitaxel was continued as monotherapy . 
 whole - body ct scans performed in october 2012 and march 2013 revealed a significant response to therapy , and the patient reported feeling well and being fully mobile . 
 no treatment - related adverse events were observed . 
 a routine brain mri scan carried out on april 18 , 2013 , revealed a recurrence of brain metastases ; however , ct scans confirmed that disease progression was not systemic , but confined to the central nervous system . 
 despite the initiation of treatment with irinotecan plus temozolomide on april 24 , the patient died on july 2 , 2013 . 
 the author believes that this case is the first report of a robust response to nab - paclitaxel monotherapy in triple - negative brca1-positive breast cancer , and that it supports further studies of nab - paclitaxel in this aggressive indication . 
Introduction
Case Report
Discussion
Disclosure Statement