Monday, December 23, 2013

Breast cancer cases predicted to increase by 44 percent in next decade

A news release from GlobalData, December 11, 2013

The total number of breast cancer cases in the United States, France, Germany, Italy, Spain, UK, Japan, urban China and Brazil is expected to increase by 44 percent over the next decade, from 0.90 million in 2012 to 1.29 million by 2022, forecasts research and consulting firm GlobalData.

According to the company’s latest report (available for only $3995!), the number of women alive five years after a diagnosis will also grow by 44 percent, climbing from 3.7 million in 2012 to 5.39 million by 2022. Out of the nine countries studied, the US and urban China had the highest number of cases five years past diagnosis in 2012, with 1.15 million and 898,406 cases, respectively.

Samantha Lee, GlobalData’s Epidemiologist, says: “The forecast growth in breast cancer incidence is partly due to rising cases of obesity, growing detection through screening programs, and changes in reproductive patterns and the use of postmenopausal hormone replacement therapy.” [The latter is not a big factor in cases of triple-negative breast cancer.]

According to the World Health Organization, increased breast cancer survival has contributed greatly to the prevalence of the disease, and there is a large body of evidence showing that breast cancer mammographic screening is effective in reducing the disease mortality by at least 20 percent in women aged 50 years and older.

“Prevention measures taken to improve breast cancer survival in parts of the world where organized nationwide mammography screening has only been made available in recent years, such as Brazil and China, will boost survival rates and impact the disease incidence and prevalence in those countries,” Lee says.

Nonetheless, GlobalData epidemiologists expect the impact of screening in these markets to be limited in the short term. This is due to the lack of sufficient resources and infrastructure needed to support the healthcare needs associated with screening, such as additional diagnostic tests and treatment.

Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

Please consider a donation to Positives About Negative to keep this site going.  This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!

Friday, December 13, 2013

SABCS: New Drug Regimens Can Lead to Improved Outcomes for Women with Stages II and III TNBC

Adding the chemotherapy drug carboplatin to standard treatment improved outcomes for women with triple-negative breast cancer in two studies presented today at the 2013 San Antonio Breast Cancer Symposium.  Both measured pathological complete response (pCR), which is recognized as a positive marker for overall survival.  The second study also showed improved outcomes using bevacizumab (Avastin).

Combining carboplatin and the targeted drug veliparib and adding the combo to standard presurgery chemotherapy nearly doubled the response rate for women with TNBC, according to results from the I-SPY 2 trial.
            In the stage II trial, 52 percent of the patients with TNBC who received veliparib, carboplatin and standard paclitaxel followed by anthracycline-based chemotherapy reached a pathological complete response (pCR).  This compared to 26 percent for those who received standard therapy alone.  Participants had tumors larger than 2.5 centimeters, so were either stage 2 or 3.
            A pCR is defined as no residual invasive cancer detected in breast tissue and lymph nodes removed during surgery, Women with a pCR have a greater chance of long-term survival compared with women who do not.  The Federal Drug Administration is increasingly using this as a measure for the approval of chemotherapy drugs.
            “These results predict that the veliparib-carboplatin regimen is highly likely to be superior to the control regimen for triple-negative breast cancer in a phase III trial,” said Hope Rugo, M.D., professor of medicine and director of breast oncology and clinical trials education at the UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco.
            This is a potent cocktail, although Rugo said most women tolerated it well.
            The research is part of an ongoing series of studies called I-SPY 2, designed to learn which patients respond better to which therapies as the trial progresses.  Those who respond well to a particular regimen remain on it; those who do not are changed to different drugs.  
            Seventy-one patients enrolled in I-SPY 2 were randomly assigned to the veliparib plus carboplatin regimen in combination with paclitaxel. Among these patients, 38 had triple-negative breast cancer and 33 had hormone receptor-positive and HER2-negative breast cancer.
CALGB/Alliance 40603
The addition of carboplatin to standard neoadjuvant chemotherapy increased the pCR in women with TNBC from 46 percent to 60 percent, according to a phase II clinical trial conducted by the CALGB/Alliance 40603.
            The research included 443 patients with operable, stage 2 or 3 triple-negative breast cancer who received carboplatin plus  standard neoadjuvant chemotherapy of pacilataxel and AC (cyclophosphamide, doxorubicin).  Surgery was performed from four to eight weeks after the completion of neoadjuvant treatment.
            The most common side effect was neutropenia, or abnormally low levels of neutrophils in the blood, leading to increased susceptibility to infection. 

Bevacizumab (Avastin)
The CALGB study also studied bevacizumab combined with standard chemotherapy and found an increased response as opposed to using standard therapy only.
Fifty-nine percent of those taking bevacizumab plus standard therapy reached  a pathological complete response as opposed to 48 percent of those on standard therapy alone. 
            “Our study was designed to find out if adding either carboplatin or bevacizumab to standard preoperative chemotherapy would increase the percentage of patients in whom cancer is eliminated before surgery,” said William M. Sikov, M.D., F.A.C.P., associate professor of medicine at the Warren Alpert Medical School of Brown University in Providence, R.I. “We are excited to report that adding either therapy significantly increased the percentage of patients in whom cancer was eliminated from the breast, and that adding both was even more effective.”
            Patients taking bevacizumab has slightly more neutropenia than those on other drugs; some also had elevated blood pressure.

Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

Please consider a donation to Positives About Negative to keep this site going.  This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!


[S5-01] Impact of the addition of carboplatin (Cb) and/or bevacizumab (B) to neoadjuvant weekly paclitaxel (P) followed by dose-dense AC on pathologic complete response (pCR) rates in triple-negative breast cancer (TNBC): CALGB 40603 (Alliance)

Sikov WM, Berry DA, Perou CM, Singh B, Cirrincione C, Tolaney S, Kuzma CS, Pluard TJ, Somlo G, Port E, Golshan M, Bellon JR, Collyar D, Hahn OM, Carey LA, Hudis C, Winer EP. Miriam Hospital and Alpert Medical School of Brown University, Providence, RI; University of Texas M.D. Anderson Cancer Center, Houston, TX; UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC; New York University Medical Center, New York, NY; Alliance Statistical Center, Durham, NC; Dana Farber Cancer Institute, Boston, MA; Southeast Cancer Control Consortium, Winston-Salem, NC; Washington University-St. Louis Medical Center, St. Louis, MO; City of Hope Comprehensive Cancer Center, Duarte, CA; Mount Sinai Medical Center, New York, NY; Patient Advocates in Research, Danville, CA; University of Chicago Medical Center, Chicago, IL; Memorial Sloan-Kettering Cancer Center, New York, NY

[S5-02] Veliparib/carboplatin plus standard neoadjuvant therapy for high-risk breast cancer: First efficacy results from the I-SPY 2 TRIAL

Rugo HS, Olopade O, DeMichele A, van 't Veer L, Buxton M, Hylton N, Yee D, Chien AJ, Wallace A, I-SPY 2 Site PI's, Lyandres J, Davis S, Sanil A, Berry D, Esserman L. University of California San Francisco Helen Diller Family Comprehensive Cancer Center; University of Chicago; University of Pennslyvania; University of Minnesota; University of Texas MD Anderson Cancer Center; I-SPY 2 Clinical Trial Sites; University of California San Diego; Berry Consultants, LLC

Thursday, December 12, 2013

SABCS: Genetic Profiles of TNBC

Research presented today at the 2013 San Antonio Breast Cancer Symposium focused on the genetic makeup of triple-negative breast cancer, which may be the best route to targeted treatment.

SOX4 and P13K
What drives tumor development?  That is especially intriguing in a disease as heterogeneous as triple-negative breast cancer.  Some answers, from an analysis of nearly 500 breast tumor samples from the TCGA project Cancer Genome Atlas Program:

• Basal-like breast cancer tumors have a high level of activity of PI3K, a cellular pathway.
• Basal-like tumors are primarily triple-negative.
• The SOX4 gene amplifies P13K
• Tumors with both PI3K and SOX4 are most likely to be aggressive and to metastasize.

Protein Kinase C
Members of the protein kinase C family are involved in proliferation, cell survival and migration, and have been implicated in the formation and production of tumors.  

• PRKCA, B, I and Q exist in higher levels in TNBC tumors.    

Primary Versus Metastatic Tumors
Does a tumor’s genetic profile change from primary cancer to metastases? In a study of 362 genetic mutations in triple-negative breast cancer, 31 were unique to the metastases—they did not exist in the original tumor.

• TNBC tumors are more likely to contain both P13K and p53.  Tumors with those genes have a less favorable prognosis and are more likely to be resistant to chemo.

• Progression-free survival was less positive with tumors than contained the genes WYNK1, P53, JAK2 and MST1.  

• This profiling can lead to targeted therapy, much of which is already underway.

Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

Please consider a donation to Positives About Negative to keep this site going.  This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!


[S4-01] An integrated genomics approach identifies novel drivers of oncogenic pathway activity in human breast cancer
Gatza ML, Silva G, Hoadley KA, Fan C, Perou CM. University of North Carolina at Chapel Hill, Chapel Hill, NC

[S4-02] Integrated genomic analyses of members of protein kinase C family identifies subtype specific alterations as novel therapeutic targets
Natrajan RC, Leonidou A, Brough R, Frankum J, Wai PT, Ng CK, Reis-Filho JS, Lord CJ, Ashworth A. The Institute of Cancer Research, London, United Kingdom; Memorial Sloan-Kettering Cancer Center, New York, NY

[S4-03] Exome sequencing reveals clinically actionable mutations in the pathogenesis and metastasis of triple negative breast cancer
Blackwell KL, Hamilton EP, Marcom PK, Peppercorn J, Spector N, Kimmick G, Hopkins J, Favaro J, Rocha G, Parks M, Love C, Scotland P, Dave SS. Duke Cancer Institute, Durham, NC; Forsyth Oncology, Winston-Salem, NC; Novant Oncology Research, Charlotte, NC

SABCS: Are Common Bone Drugs the TNBC Follow-Up Treatment We’ve Been Seeking?

They reduce the risk of bone metastases following breast cancer in post-menopausal women by 34 percent. And they reduce the risk of death in that same group by 17 percent, regardless of receptor status, node involvement or previous chemotherapy.  

They’re common bisphosphonates, drugs used to build our bones, such as Zometa and Reclast.

This could be a game changer, says Rob Coleman, M.D., who presented the findings at the 2013 San Antonio Breast Cancer Symposium today.  “We finally have defined an addition to standard treatment.”  
Coleman, of the Sheffield Cancer Research Center in England, says he is likely to recommend bisphosphonates to his postmenopausal patients.  They present “at least as large a benefit as the agents we use presently,” he says.

For triple-negative breast cancer patients, bisphosphonates may represent an elusive follow-up drug.  Because TNBC tumors are not fueled by hormones they do not respond to common post-cancer estrogen-fighting drugs  such as tamoxifen or Arimidex.

The results, part of of the Early Breast Cancer Trialists' Collaborative Group (EBCTCG)'s Bisphosphonate Working Group, represent data from multiple studies on nearly 18,000 patients. They hold true for two broad types of bisphosphonates: zoledronic acid (Zometa, Zomera, Aclasta and Reclast) or clodronates (Bonefos, Clasteon, Loron).

The results apply only to postmenopausal patients—natural or chemotherapy-induced. Premenopausal women did not see any cancer-fighting benefit from bisphosphonates.

It’s essential that bisphosphonates be given early in treatment, Coleman said.

Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

Please consider a donation to Positives About Negative to keep this site going.  This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!


[S4-07] Effects of bisphosphonate treatment on recurrence and cause-specific mortality in women with early breast cancer: A meta-analysis of individual patient data from randomized trials. 

Coleman R, Gnant M, Paterson A, Powles T, von Minckwitz G, Pritchard K, Bergh J, Bliss J, Gralow J, Anderson S, Evans V, Pan H, Bradley R, Davies C, Gray R, On Behalf of the Early Breast Cancer Trialists' Collaborative Group (EBCTCG)'s Bisphosphonate Working Group. Sheffield Cancer Research Centre