New Guidelines Might Limit Need for Lymph Node Removal for Breast Cancer

MONDAY, March 24, 2014 (HealthDay News) -- Biopsies of so-called "sentinel" lymph nodes under the arms should become more widespread among breast cancer patients, according to updated guidelines from the American Society of Clinical Oncology (ASCO).

The group, which represents cancer specialists, said the new recommendations should also restrict the number of women who will require further removal of multiple nodes after biopsy, cutting down on painful side effects.

In sentinel lymph node biopsy, a few lymph nodes are removed and checked for signs of cancer -- hence the name "sentinel." Usually, if these lymph nodes have no cancer, it means the remaining, unchecked lymph nodes should also be cancer-free.

The new ASCO recommendations expand eligibility for sentinel node biopsy and will reduce the number of patients who undergo a more invasive procedure called axillary -- underarm -- lymph node dissection, which carries a higher risk of complications, the group said.

In axillary lymph node dissection, most lymph nodes under the arm on the same side as the breast tumor are removed and examined for cancer. This procedure can cause long-term side effects such as pain and numbness in the arm and swelling due to a build-up of lymph fluid.

The new guidelines state that for women whose sentinel lymph nodes show no signs of cancer, removal of more underarm lymph nodes is not recommended.

The guidelines also addressed the case of women who undergo lumpectomy instead of full mastectomy and are also scheduled for whole-breast radiation therapy to help "mop up" residual cancer. If these patients have signs of cancer in only one or two sentinel lymph nodes upon biopsy, they too may opt to avoid further node removal, the ASCO experts said.

Women who have undergone mastectomy but show signs of cancer's spread in sentinel lymph nodes should be offered further node removal, the guidelines reaffirmed.

The ASCO also said women who are diagnosed with certain breast cancers while pregnant can skip sentinel node biopsy.

The ASCO issued initial guidelines on sentinel node biopsy in 2005. The new guidelines, published March 24 in the Journal of Clinical Oncology, are based on the findings of a panel of experts who reviewed studies published between 2004 and 2013.

"The updated guideline incorporates new evidence from more recent studies -- nine randomized controlled trials and 13 cohort studies since 2005," panel co-chairman Dr. Armando Giuliano said in an ASCO news release.

"Based on these studies, we're saying more patients can safely get sentinel node biopsy without axillary lymph node [removal]," he said. "These guidelines help determine for whom sentinel node biopsy is appropriate."

Panel co-chairman Dr. Gary Lyman said, "We strongly encourage patients to talk with their surgeon and other members of their multidisciplinary team to understand their options and make sure everybody is on the same page."

"The most critical determinant of breast cancer prognosis is still the presence and extent of lymph node involvement," he said. "Therefore, the lymph nodes need to be evaluated so we can understand the extent of the disease."

Two breast cancer specialists welcomed the new guidelines.

"Over the past few years, there has been a movement to limit the amount of axillary [lymph node] surgery in patients undergoing breast conservation," said Dr. Stephanie Bernik, chief of surgical oncology at Lenox Hill Hospital in New York City.

Bernik said the new guidelines are important because some doctors have been reluctant to move away from further underarm node removal when a patient has even one affected sentinel node. "This update will give surgeons the confidence to tell patients that a sentinel lymph node biopsy may be enough, even if there is evidence of spread, in patients undergoing [lumpectomy]," Bernik said.

"However, it is still important for surgeons to discuss the pros and cons with a patient, as not all [real-world] patients fit the study criteria," she said. "Furthermore, it needs to be stressed that the more limited surgery does not apply to women undergoing mastectomies."

Dr. Debra Patt is the medical director of an expert panel that assesses cancer care guidelines for the US Oncology Network. She said she was "thrilled" at the new ASCO guidelines because they seem to echo the results of recent studies.

"In 2010, a study presented at the ASCO annual meeting showed that women undergoing breast-conservation surgery with clinically node-negative small breast cancers could safely avoid removing all the lymph nodes from under the arm in most cases," Patt said. "There has been greater variance in treatment patterns in my community practice, and I believe these updated guidelines will direct practitioners to evidence-based patient care."

-- Robert Preidt
Copyright © 2014 HealthDay. All rights reserved. SOURCES: Stephanie Bernik, M.D., chief, surgical oncology, Lenox Hill Hospital, New York City; Debra Patt, M.D., medical director, Pathways Task Force and Healthcare Informatics, US Oncology Network; American Society of Clinical Oncology, news release, March 24, 2014

View the original article here

Genetics Home Reference: fragile XE syndrome

Fragile XE syndrome is a genetic disorder that impairs thinking ability and cognitive functioning. Most affected individuals have mild intellectual disability. In some people with this condition, cognitive function is described as borderline, which means that it is below average but not low enough to be classified as an intellectual disability. Females are rarely diagnosed with fragile XE syndrome, likely because the signs and symptoms are so mild that the individuals function normally.

Learning disabilities are the most common sign of impaired cognitive function in people with fragile XE syndrome. The learning disabilities are likely a result of communication and behavioral problems, including delayed speech, poor writing skills, hyperactivity, and a short attention span. Some affected individuals display autistic behaviors, such as hand flapping, repetitive behaviors, and intense interest in a particular subject. Unlike some other forms of intellectual disability, cognitive functioning remains steady and does not decline with age in fragile XE syndrome.

Fragile XE syndrome is estimated to affect 1 in 25,000 to 100,000 newborn males. Only a small number of affected females have been described in the medical literature. Because mildly affected individuals may never be diagnosed, it is thought that the condition may be more common than reported.

Fragile XE syndrome is caused by mutations in the AFF2 gene. This gene provides instructions for making a protein whose function is not well understood. Some studies show that the AFF2 protein can attach (bind) to DNA and help control the activity of other genes. Other studies suggest that the AFF2 protein is involved in the process by which the blueprint for making proteins is cut and rearranged to produce different versions of the protein (alternative splicing). Researchers are working to determine which genes and proteins are affected by AFF2.

Nearly all cases of fragile XE syndrome occur when a region of the AFF2 gene, known as the CCG trinucleotide repeat, is abnormally expanded. Normally, this segment of three DNA building blocks (nucleotides) is repeated approximately 4 to 40 times. However, in people with fragile XE syndrome, the CCG segment is repeated more than 200 times, which makes this region of the gene unstable. (When expanded, this region is known as the FRAXE fragile site.) As a result, the AFF2 gene is turned off (silenced), and no AFF2 protein is produced. It is unclear how a shortage of this protein leads to intellectual disability in people with fragile XE syndrome.

People with 50 to 200 CCG repeats are said to have an AFF2 gene premutation. Current research suggests that people with a premutation do not have associated cognitive problems.

Read more about the AFF2 gene.

Fragile XE syndrome is inherited in an X-linked dominant pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. In males (who have only one X chromosome), a mutation in the only copy of the gene in each cell causes the disorder. In most cases, males experience more severe symptoms of the disorder than females.

In parents with the AFF2 gene premutation, the number of CCG repeats can expand to more than 200 in cells that develop into eggs or sperm. This means that parents with the premutation have an increased risk of having a child with fragile XE syndrome. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons; sons receive a Y chromosome from their father, which does not include the AFF2 gene.

These resources address the diagnosis or management of fragile XE syndrome and may include treatment providers.

You might also find information on the diagnosis or management of fragile XE syndrome in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

You may find the following resources about fragile XE syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

FRAXE intellectual deficitFRAXE intellectual disabilityFRAXE mental retardation syndromeFRAXE syndromemental retardation, X-linked, associated with fragile site FRAXEmental retardation, X-linked, FRAXE type

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

View the original article here

Genetics Home Reference: hereditary diffuse gastric cancer

Hereditary diffuse gastric cancer (HDGC) is an inherited disorder that greatly increases the chance of developing a form of stomach (gastric) cancer. In this form, known as diffuse gastric cancer, there is no solid tumor. Instead cancerous (malignant) cells multiply underneath the stomach lining, making the lining thick and rigid. The invasive nature of this type of cancer makes it highly likely that these cancer cells will spread (metastasize) to other tissues, such as the liver or nearby bones.

Symptoms of diffuse gastric cancer occur late in the disease and can include stomach pain, nausea, vomiting, difficulty swallowing (dysphagia), decreased appetite, and weight loss. If the cancer metastasizes to other tissues, it may lead to an enlarged liver, yellowing of the eyes and skin (jaundice), an abnormal buildup of fluid in the abdominal cavity (ascites), firm lumps under the skin, or broken bones.

In HDGC, gastric cancer usually occurs in a person's late thirties or early forties, although it can develop anytime during adulthood. If diffuse gastric cancer is detected early, the survival rate is high; however, because this type of cancer is hidden underneath the stomach lining, it is usually not diagnosed until the cancer has become widely invasive. At that stage of the disease, the survival rate is approximately 20 percent.

Some people with HDGC have an increased risk of developing other types of cancer, such as a form of breast cancer in women that begins in the milk-producing glands (lobular breast cancer); prostate cancer; and cancers of the colon (large intestine) and rectum, which are collectively referred to as colorectal cancer. Most people with HDGC have family members who have had one of the types of cancer associated with HDGC. In some families, all the affected members have diffuse gastric cancer. In other families, some affected members have diffuse gastric cancer and others have another associated form of cancer, such as lobular breast cancer. Frequently, HDGC-related cancers develop in individuals before the age of 50.

Gastric cancer is the fourth most common form of cancer worldwide, affecting 900,000 people per year. HDGC probably accounts for less than 1 percent of these cases.

It is likely that 30 to 40 percent of individuals with HDGC have a mutation in the CDH1 gene. The CDH1 gene provides instructions for making a protein called epithelial cadherin or E-cadherin. This protein is found within the membrane that surrounds epithelial cells, which are the cells that line the surfaces and cavities of the body. E-cadherin helps neighboring cells stick to one another (cell adhesion) to form organized tissues. E-cadherin has many other functions including acting as a tumor suppressor protein, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way.

People with HDGC caused by CDH1 gene mutations are born with one mutated copy of the gene in each cell. These mutations cause the production of an abnormally short, nonfunctional version of E-cadherin or alter the protein's structure. For diffuse gastric cancer to develop, a second mutation involving the other copy of the CDH1 gene must occur in the cells of the stomach lining during a person's lifetime. People who are born with one mutated copy of the CDH1 gene have a 70 percent chance of acquiring a second mutation in the other copy of the gene and developing gastric cancer in their lifetimes.

When both copies of the CDH1 gene are mutated in a particular cell, that cell cannot produce any functional E-cadherin. The loss of this protein prevents it from acting as a tumor suppressor, contributing to the uncontrollable growth and division of cells. A lack of E-cadherin also impairs cell adhesion, increasing the likelihood that cancer cells will not come together to form a tumor but will invade the stomach wall and metastasize as small clusters of cancer cells into nearby tissues.

These CDH1 gene mutations also lead to a 60 percent chance of lobular breast cancer, a slightly increased risk of prostate cancer in men, and a slightly increased risk of colorectal cancer. It is unclear why CDH1 gene mutations primarily occur in the stomach lining and these other tissues.

About 60 to 70 percent of individuals with HDGC do not have an identified mutation in the CDH1 gene. The cancer-causing mechanism in these individuals is unknown.

Read more about the CDH1 gene.

HDGC is inherited in an autosomal dominant pattern, which means one copy of the altered CDH1 gene in each cell is sufficient to increase the risk of developing cancer.

In most cases, an affected person has one parent with the condition.

These resources address the diagnosis or management of hereditary diffuse gastric cancer and may include treatment providers.

You might also find information on the diagnosis or management of hereditary diffuse gastric cancer in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

You may find the following resources about hereditary diffuse gastric cancer helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

E-cadherin-associated hereditary gastric cancerfamilial diffuse gastric cancerFDGCHDGChereditary diffuse gastric adenocarcinoma

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

View the original article here

Genetics Home Reference: megalencephaly-capillary malformation syndrome

Megalencephaly-capillary malformation syndrome (MCAP) is a disorder characterized by overgrowth of several tissues in the body. Its primary features are a large brain (megalencephaly) and abnormalities of small blood vessels in the skin called capillaries (capillary malformations).

In individuals with MCAP, megalencephaly leads to an unusually large head size (macrocephaly), which is typically evident at birth. After birth, the brain and head continue to grow at a fast rate for the first few years of life; then, the growth slows to a normal rate, although the head remains larger than average. Additional brain abnormalities are common in people with MCAP; these can include excess fluid within the brain (hydrocephalus) and abnormalities in the brain's structure, such as those known as Chiari malformation and polymicrogyria. Abnormal brain development leads to intellectual disability in most affected individuals and can also cause seizures or weak muscle tone (hypotonia). In particular, polymicrogyria is associated with speech delays and difficulty chewing and swallowing.

The capillary malformations characteristic of MCAP are composed of enlarged capillaries that increase blood flow near the surface of the skin. These malformations usually look like pink or red spots on the skin. In most affected individuals, capillary malformations occur on the face, particularly the nose, the upper lip, and the area between the nose and upper lip (the philtrum). In other people with MCAP, the malformations appear as patches spread over the body or as a reddish net-like pattern on the skin (cutis marmorata).

In some people with MCAP, excessive growth affects not only the brain but other individual parts of the body, which is known as segmental overgrowth. This can lead to one arm or leg that is bigger or longer than the other or a few oversized fingers or toes. Some affected individuals have fusion of the skin between two or more fingers or toes (cutaneous syndactyly).

Additional features of MCAP can include flexible joints and skin that stretches easily. Some affected individuals are said to have doughy skin because the tissue under the skin is unusually thick and soft.

The gene involved in MCAP is also associated with several types of cancer. Although a small number of individuals with MCAP have developed tumors (in particular, a childhood form of kidney cancer known as Wilms tumor and noncancerous tumors in the nervous system known as meningiomas), people with MCAP do not appear to have a greater risk of developing cancer than the general population.

These resources address the diagnosis or management of megalencephaly-capillary malformation syndrome and may include treatment providers.

You might also find information on the diagnosis or management of megalencephaly-capillary malformation syndrome in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

You may find the following resources about megalencephaly-capillary malformation syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

The Handbook provides basic information about genetics in clear language.

These links provide additional genetics resources that may be useful.

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

View the original article here