Cancer Treatment Today » Breast Cancer

BREVAgen

M Levin, MD — Fri, 03 Jan 2014 14:39:58 +0000

Personalized medicine is an up and coming approach, by which individual’s risks and factors are taken into account to prescribe therapy. Genetic tests are a part of the approach. BREVAGen evaluates 7 breast cancer-associated factors. Risk is calculated by multiplying the product of the individual risks by the Gail model risk The Gail model is the first of several proposed ways to calcucalte an individual’s riask for breast cancer. BREVAGen has been evaluated for use in Caucasian women of European descent age 35 years and older. According to the BREVAGen website, “suitable candidates” for testing include women with a Gail lifetime risk of 15% or greater; with high lifetime estrogen exposure (e.g., early menarche and late menopause); or with relatives diagnosed with breast cancer. BREVAGen is not suitable for women with previous diagnoses of lobular carcinoma in situ, ductal carcinoma in situ, or breast cancer, since the Gail model cannot calculate breast cancer risk accurately for such women, or for women with an extensive family history of breast and ovarian cancer.

BREVAgen was validated only in comparison to Gail score. Being that the Gail score is the least sensitive scoring tool available and that it is widely considered inadequate, it is hard to have confidence in the validation process. In addition, the risk calculation that depends on multiplying SNP risks by Gail raises its own questions of accuracy. Finally, there is no prospective evidence that BREVAgen produces clinical evidence.

Faslodex for breast cancer

M Levin, MD — Sun, 03 Feb 2013 17:59:16 +0000

Fulvestrant is FDA indicated for the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy. (Faslodex)Fulvestrant is a hormonal treatment that works differently than other hormonal treatments. It acts not by competing with estrogen but by selectively down modulating it and causing it to be degraded and disappear. It used to be thought that this unique mechanism of action gives fulvestrant greater efficacy than other hormonal treatments but that does not appear to be the case. Four comparative clinical trials showed similar efficacy to the other hormonal agents (aromatase inhibitors and tamoxifen) with good tolerability profile. Nevertheless, Fulvestrant provided effective second-line therapy in this setting for postmenopausal women who had relapsed or progressed after previous endocrine therapy.

One might wonder then if fulvestrant has anything to recommend it in first line, especially since it is very often used in that line. For this reason,creating quite a stir, the U.K. National Institute for Health and Clinical Excellence (NICE) said in 2011 that it found no evidence Faslodex was significantly better than existing treatments, and it did not recommend its routine use in the country’s National Health Service. It is a more convenient drug in some situations, since it is an injectable drug that is administered once monthly. There are patients, especially in institutional setting, such as nursing homes, for whom once monthly fulvestrant is more realistic than either IV or daily oral drugs.

Fulvestrant In combinations is discussed in the Professional version.

For Professional version see here

Pain is not suffering

M Levin, MD — Mon, 03 Dec 2012 03:41:52 +0000

Questions of theodicy (why bad things happen to good people) are often predicated on an inadequate understanding of the distinction between pain and suffering. The two are different and distinct. The concept of suffering has been extensively analyzed in the medical and bio-ethical literature. Much of this work was done by Cassel.

in brief, the relevant point is that there is a distinction between pain and suffering. Life often brings with it pain, but suffering is existential. Pain is value neutral and can even be a positive experience. Suffering, on the other hand, requires an interpretation of pain. Thus, for example, childbirth is pain but nor suffering, for it is a happy, meaningful occasion, whereas chronic back pain is suffering because it is purposeless and is so perceived. Consequently, as we often observe, even minor pain can lead to disproportional suffering, when it is interpreted as a meaningless and triggers hopelessness, helplessness, and loss of worth. On the other hand, suffering can be turned into… just a pain, if it can interpreted as meaningful and beneficial. This teaches us that one’s perceptions and interpretations of pain can make it a tolerable means to some meaningful benefit, or can turn it into exquisite suffering.

If so, animals cannot suffer for they cannot judge or interpret pain. Animal rights may differ but we are talking philosophically. Sure, animals feel pain. People under anesthesia also often feel pain; their heart rate and blood pressure can be demonstrated to go up, especially when anesthesia is light, but they do not suffer because their cerebrums are turned off. The question why animals suffer pain, however, is of a different magnitude of impact than the one of why they undergo suffering.

Irinotecan for brain metastases of lung and breast cancer

M Levin, MD — Fri, 09 Nov 2012 15:38:40 +0000

Because irinotecan penetrates the brain-blood barrier and has an effect in primary brain cancer, there is some interest in using it for brain metastasis, especially for lung cancer and breast cancer. Most studies of irinotecan had been for brain mets of small(SCLC) and non-small cell lung cancer(NSMCLC) and not breast cancer and have had mixed results. One study enrolled several different cancer types and reported complete responses with irinotecan-based chemotherapy for brain metastases in three patients with SCLC, parotid cancer, and esophageal adenocarcinoma. The combination of cisplatin, ifosfamide and irinotecan in treatment-naive patients with NSCLC led to a response rate in the brain of 50%. A study of temozolomide (200 mg/m²) on days 1 to 5 and irinotecan (200 mg/m²) on days 1 to 5 every 4 weeks in previously untreated patients with NSCLC brain metastases reported no responses.

There are several ongoing studies for lung cancer. For breast cancer, there is also a study: Irinotecan and Temozolomide in Treating Patients With Breast Cancer Who Have Received Previous Treatment for Brain Metastases, NCT00617539.

For Professional version see here

PET is staging metastases to the axillae(armpits)

M Levin, MD — Mon, 29 Oct 2012 14:54:34 +0000

It is generally accepted that stage I and II breast cancer does not require staging for distant metastases. Stage II is divided into stage IIA and stage IIB based on tumor size and whether it has spread to the axillary lymph nodes (the lymph nodes under the arm). In stage IIA, the cancer is either not larger than 2 centimeters and has spread to the axillary lymph nodes, or between 2 and 5 centimeters but has not spread to the axillary lymph nodes. In stage IIB, the cancer is either between 2 and 5 centimeters and has spread to the axillary lymph nodes, or larger than 5 centimeters but has not spread to the axillary lymph nodes. Whether axillae are involved is determined by physical exam, nodal dissection or, more recently, by sentinel node procedures or imaging and/or biopsy. It is tempting to use PET ro find lymph node invovlement but, unfortunately, PET is not very good for this purpose.

The sensitivity of PEt to stage axillae is limited. A multicenter trial cast doubt on the early supportive studies, and more recent single-center trials performed in the era of sentinel lymph node mapping showed that, compared with sentinel lymph node biopsy, the sensitivity of FDG PET and PET/CT for axillary nodal metastases was as low as 20%–40%. Therefore, PET should not be used as an axillary staging modality

For Professional version see here

Taxotere and Cytoxan for metastatic breast cancer

M Levin, MD — Thu, 18 Oct 2012 02:43:03 +0000

Preclinical data demonstrate in vitro synergy for combinations of docetaxel (Taxotere) and cyclophosphamide. As single agents, both drugs have proven highly active against breast cancer, and the activity of the combination has been confirmed by several phase II studies. More recently, it has proven adjuvant efficacy on par with anthracycline containing regimen in a trial to directly compare AC to Taxotere/Cytoxan (TC) as adjuvant treatment in breast cancer. This recent trial showed that TC improves disease-free survival compared with AC for the treatment of adjuvant breast cancer. Although cardiac side effects were not presented, the researcher noted that TC does not appear to have the cardiotoxicity issues associated with AC, which is a very important issue for some patients. NCCN considers TC an appropriate regimen for adjuvant treatment for breast cancer. and NCCN 2012 lists this regimen on p. BINV-K.However, NCCN does not list it for metastatic disease.

For the Professional version see here

Bioimpedance testing for lymphedema

M Levin, MD — Thu, 11 Oct 2012 16:33:08 +0000

Breast cancer-related lymphedema (BCRL) is a chronic, debilitating disorder that is frequently misdiagnosed, treated too late or not treated at all. Being able to quantitively follow it or predict its onset or severity would be clinically useful. Bioimpedance is one method of obtaining scores that may prove predictive with followup and over time.

The L-Dex XCA is a bioimpedance analyzer designed to assist in the clinical assessment of unilateral lymphedema of the arm. The L-Dex XCA utilizes a simple linear scale called the L-Dex (lymphedema index). The L-Dex ranges from -10 to +10 and defines the normal range of L-Dex values for a patient without lymphedema. The presence or absence of lymphedema is assessed by comparing the patient’s L-Dex to this range.

The National Lymphedema Network position statement, Screening and Measurement for Early Detection of Breast Cancer Related Lymphedema, updated April 2011, states that circumferential tape measurements are acceptable means of measuring limb volume. The current position statement states “bioelectrical spectroscopy (BIS) or infrared perometry are suggested as alternative or adjunctive methods to circumferential measurement.” A technology assessment of the diagnosis and management of secondary lymphedema prepared for the Agency for Healthcare Research and Quality (Oremus et al, 2010) concluded: “There is consistent evidence to indicate that lymphedema can be reliably measured using circumferential measures or volume displacement … There is too little evidence to draw conclusions about the reliability of other tests such as tonometry, ultrasound, lymphoscintigraphy, or bioimpedance.” The Northern Ireland CREST Committee guidelines for lymphedema (2008) recommend circumferential limb volume measurement for assessing limb volume. Bioimpedance measurement is described as promising, noting that it should be considered over the next 5 years. Presumably, an updates statemetns will soon be issued.
by Shah et al says that However the most recent guideline says that Bioimpedance spectroscopy represents a standard diagnostic approach to assess for breast cancer-related lymphedema, allowing for early detection and treatment. BIS should be used as part of routine clinical care starting with measurement prior to treatment; however, BCRL surveillance can be utilized without a pre-treatment assessment. The updated clinical practice guidelines are supported by evidence from a randomized controlled trial and other real-world data.

Torgbenu E, Luckett T, Buhagiar MA, Phillips JL. Guidelines Relevant to Diagnosis, Assessment, and Management of Lymphedema: A Systematic Review. Adv Wound Care (New Rochelle). 2023 Jan;12(1):15-27. doi: 10.1089/wound.2021.0149.

The National Cancer Institute Physician Data Query (PDQ) on lymphedema (NCI, 2011) states that circumferential upper-extremity measurement is the most widely used method to diagnose upper-extremity lymphedema. Bioimpedance is listed among several other options for evaluating limb volume. The PDQ also stated that a study comparing various methods of assessing upper-limb lymphedema did not show any superiority of any one method; for support, the PDQ cited a study by Ridner, et al. (2007) comparing circumferential limb measurements to bioimpedance and perometry.
n the balance, there is some support in guideliens for the concept of testing for the risk of lymphedema over time, but specifically bioimpedance appears not to be well supported.

Shah C, Whitworth P, Valente S, Schwarz GS, Kruse M, Kohli M, Brownson K, Lawson L, Dupree B, Vicini FA. Bioimpedance spectroscopy for breast cancer-related lymphedema assessment: clinical practice guidelines. Breast Cancer Res Treat. 2023 Feb;198(1):1-9.

Treating with chemotherapy before surgery for breast cancer

M Levin, MD — Fri, 28 Sep 2012 18:21:10 +0000

Neoadjuvant chemotherapy came into vogue in the seventies and eighties, spurred on by the success of organ preservation strategies in cancers such as laryngeal and rectal cancer. It used to be thought there are two potential benefits of neoadjuvant chemotherapy: downstaging a breast tumor so lesser surgery can be performed – lumpectomy instead of mastectomy, and to potentially treat early occult metastatic disease and to improve survival. The first goal can be successfully accomplished as has has been corroborated by large randomized studies but the second goal has not been proven to be accomplished by neaodjuvant chemotherapy. In fact, studies do not show a that women live longer after neaodjuvant chemotherapy. However, more recently, with improving chemotherapy effectiveness, it became appreciated that response is a predictive tool that can be used to plan farther chemotherapy. The idea is the giving chemo first can identify patients who need a more aggressive approach. However, NCCN still only recommends neoadjuvant therapy for women in stage IIA or higher and who desire breast preservation.

For Professional version see here

Tykerb and Taxol for metastatic breast cancer

M Levin, MD — Tue, 18 Sep 2012 20:39:08 +0000

The Taxol and Tykerb combination has recently been shown to improve quality of life in metastatic breast cancer patients versus Taxol alone. In a phase 3 randomized, multicenter, double-blind, placebo-controlled study, first-line therapy with Tykerb plus Taxol significantly improved clinical outcomes based on a pre-planned. The combination of investigational Tykerb (lapatinib) and Taxol (paclitaxel) as neoadjuant chemotherapy appears effective against inflammatory breast cancer, according to another small study. There are, as of yet in 2012, no published Phase III studies on survival for this regimen.

NCCN does not list the Taxol/Tykerb regimen.

Read the Professional version here.

Breast tomosynthesis: a new mammography

M Levin, MD — Fri, 24 Aug 2012 17:59:49 +0000

Breast tomosynthesis is a 3-dimensional (3-D) imaging technology that involves acquiring images of a compressed breast at multiple angles during a short scan. It is more comfortable than standard mammography. The individual images are then reconstructed into a series of thin high-resolution slices that displayed individually or in a dynamic movie-like mode. Tomosynthesis can reduce or eliminate the tissue overlap effect. While holding the breast stationary, images are acquired at a number of different x-ray source angles. Objects at different heights in the breast project differently for each angle. The final step in the tomosynthesis procedure takes advantage of this fact and reconstructs the data to generate images that enhance objects from a given height by appropriate shifting of the projections relative to one another. Tomosynthesis has many properties that make it suitable as a modality for screening, including good diagnostic performance, short examination time and low radiation dose. It may become a strong competitor to the current gold standard breast screening modality, i.e. mammography. At the same time, theoretical advantages have not yet been shown to translate into clinical advantage or even equivalence to standard mammography.

Read the Professional version here.