Circulating Tumor Cells Culture Promises Individualized Testing and Treatment

Yu et al in their paper in Science report that ex-vivo culture of breast circulating tumor cells (CTC) collected from patients over the course of their treatment allows for individualized treatment.   The researchers drew blood from women with breast cancer, isolated cancer cells in their blood, and tested which drugs might effectively halt the cancer. The technique consists of applying a magnetic coating on white blood cells and use magnets to select out the tumor cells for testing. These cells could then be used to grow tumors in laboratory dishes and in mice.  In their proof-of-concept study, they established CTC cultures from six patients with estrogen receptor–positive breast cancer. Three of five CTC lines tested were tumorigenic in mice.  Circulating tumor cells were present at low concentrations in the peripheral blood of those patients.  Genome sequencing of the CTC lines revealed preexisting mutations in the PIK3CA gene and newly acquired mutations in the estrogen receptor gene (ESR1), PIK3CA gene, and fibroblast growth factor receptor gene (FGFR2), among others. The method needs to be refined as only six out of 36 samples with breast cancer could be successfully grown in a dish.  It has been proposed that ex vivo culture and characterization of CTCs may provide an opportunity to noninvasively monitor the changing patterns in individual patients as their tumors acquire new mutations.  The authors suggest that drug sensitivity testing of CTC lines with multiple mutations revealed potential new therapeutic targets. With optimization of CTC culture, this strategy may help identify the best therapies for individual patients with cancer over the course of their disease with a simple blood draw instead of performing invasive biopsies or imaging studies that can be non-specific.  As cancer treatments require continuous adjustments oncologists need a noninvasive way to collect tumor cells from patients over the course of the treatment and decide when to replace a drug that worked initially but lost its potency as the tumor acquired new mutations. If the method becomes reliable and can be used to to grow cells from other types of cancer it has the potential to become a major advance in clinical oncology.

Ultrasound as an adjunct to mammography detects more cancers in women with dense breasts

Scheel et al study published in AJOG, reports on their review from 189 studies of screening for breast cancer in women with dense breasts.  From the total of 189 studies, 12 that were conducted between January 2000 and April 2013 met the criteria set by the researchers. The reporting of breast cancer risk factors varied across studies; however, the populations studied tended to be at greater than average risk for developing breast cancer.

Overall, ultrasound (US) detected an additional 0.3-7.7 cancers/1,000 examinations (Median 4.2) and was associated with an additional 11.7-106.6 biopsies/1,000 examinations (Median 52.2). They found that US screening for women with dense breast tissue increases cancer detection and leads to fewer false positive biopsies compared to mammography alone.

The researchers report that most of the additional cancers identified by ultrasound were small and node-negative stage. Such cancers can be curable and require less aggressive treatment because of the early detection. They suggest physicians should discuss the use of ultrasound as an adjunct to mammography with patients who have dense breast tissues.  They should explain the benefits and also potential to lead to additional percutaneous biopsies in easy to understand terms and arrive at a shared decision consistent with individual patient’s preferences and values.

The analysis of data from the reviewed studies suggest that potential benefits and harms could accrue if screening ultrasound is added to mammographic screening of women with dense breast tissue.

DOI: http://dx.doi.org/10.1016/j.ajog.2014.06.048

Red meat increases the incidence of breast cancer in young women

Farvid et al report in BMJ findings from their study of responses to a questionnaire of 88,803 premenopausal women from the Nurses’ Health Study II regarding their diet that were completed in1991.  Their analysis found 2830 cases of breast cancer during 20 years of follow-up.

Higher intake of red meat was associated with an increased risk of breast cancer overall (relative risk 1.22, 95% CI 1.06 to 1.40). However, higher intakes of poultry, fish, eggs, legumes, and nuts were not related to breast cancer overall.

When the association was evaluated by menopausal status, higher intake of poultry was associated with a lower risk of breast cancer in postmenopausal women (0.73, 0.58 to 0.91) but not in premenopausal women.

In estimating the effects of exchanging different protein sources, substituting one serving/day of legumes for one serving/day of red meat was associated with a 15% lower risk of breast cancer among all women (0.85, 0.73 to 0.98) and a 19% lower risk among premenopausal women (0.81, 0.66 to 0.99). Also, substituting one serving/day of poultry for one serving of red meat lower the overall risk of breast cancer (0.83, 0.72 to 0.96) and a 24% lower risk of postmenopausal breast cancer (0.76, 0.59 to 0.99). Furthermore, substituting one serving/day of combined legumes, nuts, poultry, and fish for one serving/day of red meat was associated with a 14% lower risk of breast cancer overall (0.86, 0.78 to 0.94).

The authors conclude that higher consumption of red meat by young women is a risk factor for breast cancer.  They also state that replacing red meat with a combination of legumes, poultry, nuts and fish may reduce the risk of breast cancer.

Tomosynthesis detects more breast cancers

Friedewald at al report in a JAMA article a retrospective analysis of performance metrics of Tomosynthesis and Digital Mammography from 13 academic and nonacademic breast centers.  

Patients were studied under two different protocols: those who had digital mammography screening alone and those who in addition to digital mammography, tomosynthesis was added .

A total of 454 850 examinations (n=281 187 digital mammography; n=173 663 digital mammography + tomosynthesis) were evaluated. With digital mammography, 29 726 patients were recalled and 5056 biopsies resulted in cancer diagnosis in 1207 patients (n=815 invasive; n=392 in situ). With digital mammography + tomosynthesis, 15 541 patients were recalled and 3285 biopsies resulted in cancer diagnosis in 950 patients (n=707 invasive; n=243 in situ). Model-adjusted rates per 1000 screens were as follows: for recall rate, 107 (95% CI, 89-124) with digital mammography vs 91 (95% CI, 73-108) with digital mammography + tomosynthesis; difference, –16 (95% CI, –18 to –14; P < .001); for biopsies, 18.1 (95% CI, 15.4-20.8) with digital mammography vs 19.3 (95% CI, 16.6-22.1) with digital mammography + tomosynthesis; difference, 1.3 (95% CI, 0.4-2.1; P = .004); for cancer detection, 4.2 (95% CI, 3.8-4.7) with digital mammography vs 5.4 (95% CI, 4.9-6.0) with digital mammography + tomosynthesis; difference, 1.2 (95% CI, 0.8-1.6; P < .001); and for invasive cancer detection, 2.9 (95% CI, 2.5-3.2) with digital mammography vs 4.1 (95% CI, 3.7-4.5) with digital mammography + tomosynthesis; difference, 1.2 (95% CI, 0.8-1.6; P < .001). The in situ cancer detection rate was 1.4 (95% CI, 1.2-1.6) per 1000 screens with both methods. Adding tomosynthesis was associated with an increase in the positive predictive value for recall from 4.3% to 6.4% (difference, 2.1%; 95% CI, 1.7%-2.5%; P < .001) and for biopsy from 24.2% to 29.2% (difference, 5.0%; 95% CI, 3.0%-7.0%; P < .001).

The authors conclude the addition of tomosynthesis to digital mammography was associated with a decrease in recall rate and an increase in cancer detection rate.

An editorial by Drs. Pisano and Yaffe on Tomosynthesis appears in the same issue of JAMA.