Tumor

When the tissue sample is inspected grossly, the tumor is measured in three dimensions using a ruler and the distance to all the margins of excision are recorded. Other observation such as the presence of satellite nodules, tumor necrosis (death tissue), calcifications, relationship with the skin, nipple or deep fascia etc are recorded. The presence of other possible non-cancerous lesions are described. Ultimately, samples of the tumor, margins, other lesions etc. are taken and submitted for microscopic examination. When the tissue sample is inspected grossly, the tumor is measured in three dimensions using a ruler and the distance to all the margins of excision are recorded. Other observation such as the presence of satellite nodules, tumor necrosis (death tissue), calcifications, relationship with the skin, nipple or deep fascia etc are recorded. The presence of other possible non-cancerous lesions are described. Ultimately, samples of the tumor, margins, other lesions etc. are taken and submitted for microscopic examination.

There are multiple parameters used to determine the tumor aggressiveness. Some are histological, some molecular some clinical.

The histologic indicators are: tumor size, tumor histology, tumor differentiation, lymphovascular invasion, multi-focality, and number of mitosis.

Molecular parameters include expression of estrogen and progesterone hormonal receptors; expression of HER2-neu; proliferative activity of the tumor (Ki67, mitosis) and other genetic profiles of the tumor cells as determine by molecular analysis of the cells via RNA or DNA studies such as Oncotype, Mamotomme etc. that provide a “genetic signature” of the tumor cells able to predict the aggressiveness of the tumor and guide to a certain extent the therapeutic approach.

Clinical parameters relate to the clinical and imaging findings such as palpable lymph nodes, positive scans for probable metastasis, etc.

Smaller and single size (<2 cm) tumors with pure mucinous or tubular type of histology or other histology that is well differentiated (grade 1), with no vascular/lymphatic invasion, and ER/PR positive with no overexpression of Her2 neu would be the least aggressive tumors. However, the histologic/molecular parameters are secondary to the stage of the tumor as given by the TNM staging.

Cancer staging system is routinely used to summarize some histologic/clinical characteristics of the tumors. The staging includes three letters: T is for Tumor size; N is for lymph Node metastasis and M is for distant organ Metastasis. Of the four possible stages, Stage 1 will have the best prognosis since the tumors in this group are small and there is no nodal or distant organ metastasis. It is only within the same stage that the histologic and molecular indicator acquire larger relevance. There are multiple parameters used to determine the tumor aggressiveness. Some are histological, some molecular some clinical.

The histologic indicators are: tumor size, tumor histology, tumor differentiation, lymphovascular invasion, multi-focality, and number of mitosis.

Molecular parameters include expression of estrogen and progesterone hormonal receptors; expression of HER2-neu; proliferative activity of the tumor (Ki67, mitosis) and other genetic profiles of the tumor cells as determine by molecular analysis of the cells via RNA or DNA studies such as Oncotype, Mamotomme etc. that provide a “genetic signature” of the tumor cells able to predict the aggressiveness of the tumor and guide to a certain extent the therapeutic approach.

Clinical parameters relate to the clinical and imaging findings such as palpable lymph nodes, positive scans for probable metastasis, etc.

Smaller and single size (<2 cm) tumors with pure mucinous or tubular type of histology or other histology that is well differentiated (grade 1), with no vascular/lymphatic invasion, and ER/PR positive with no overexpression of Her2 neu would be the least aggressive tumors. However, the histologic/molecular parameters are secondary to the stage of the tumor as given by the TNM staging.

Cancer staging system is routinely used to summarize some histologic/clinical characteristics of the tumors. The staging includes three letters: T is for Tumor size; N is for lymph Node metastasis and M is for distant organ Metastasis. Of the four possible stages, Stage 1 will have the best prognosis since the tumors in this group are small and there is no nodal or distant organ metastasis. It is only within the same stage that the histologic and molecular indicator acquire larger relevance.

This is an excellent question. Caris is a member of a group of molecular profiling companies. These groups extract protein, DNA or RNA and measure the genetic information present in fixed tissue. Their intent is to match patients to therapy based on this static data. That is, the presence of a gene should, according to their reasoning, confer sensitivity to a drug. The proof of this concept, however, is sorely lacking. If we examine one publication in the literature (VonHoff D et al, J Clin Oncol Nov 2010), we find an objective response rate (measurable benefit in 66 patients treated using molecularly selected drugs) of 10%. Indeed, the positive results reported in this study reflected not a response rate but instead a 30% improvement in the time to disease progression, associated with molecular drug selection, compared with the patients prior, most recent (unsuccessful) therapies. To put this in context, a patient could arguably fail a physician-selected treatment after 1 month, and then receive a Caris selected therapy. If they responded for 1 month plus 10 days (a 30% improvement), they were counted as a success. The clinical relevance of that degree of improvement seems questionable.
While we fully understand the excitement surrounding genetic analyses, the more sophisticated researchers in the field are beginning to appreciate that the complexity of human biology demands more global (functional) analytic platforms that encompass all of the mechanisms of response and resistance. In this light, the presence of a gene cannot predict whether that gene will be expressed, active, counter-acted by a complementary gene, or functional.
We believe that human biology must be taken at face value in its most complex state. This is known as the phenotype and must be examined for the biological features that these interconnected cellular systems create. This field now known as biosystematics, or systems biology, recognizes the redundancies and uncertainties that separate the genotype (molecular profiling) from the phenotype (functional analyses) are not trivial. Our laboratory conducts phenotype analyses. Caris conducts genotype analyses. This is an excellent question. Caris is a member of a group of molecular profiling companies. These groups extract protein, DNA or RNA and measure the genetic information present in fixed tissue. Their intent is to match patients to therapy based on this static data. That is, the presence of a gene should, according to their reasoning, confer sensitivity to a drug. The proof of this concept, however, is sorely lacking. If we examine one publication in the literature (VonHoff D et al, J Clin Oncol Nov 2010), we find an objective response rate (measurable benefit in 66 patients treated using molecularly selected drugs) of 10%. Indeed, the positive results reported in this study reflected not a response rate but instead a 30% improvement in the time to disease progression, associated with molecular drug selection, compared with the patients prior, most recent (unsuccessful) therapies. To put this in context, a patient could arguably fail a physician-selected treatment after 1 month, and then receive a Caris selected therapy. If they responded for 1 month plus 10 days (a 30% improvement), they were counted as a success. The clinical relevance of that degree of improvement seems questionable.
While we fully understand the excitement surrounding genetic analyses, the more sophisticated researchers in the field are beginning to appreciate that the complexity of human biology demands more global (functional) analytic platforms that encompass all of the mechanisms of response and resistance. In this light, the presence of a gene cannot predict whether that gene will be expressed, active, counter-acted by a complementary gene, or functional.
We believe that human biology must be taken at face value in its most complex state. This is known as the phenotype and must be examined for the biological features that these interconnected cellular systems create. This field now known as biosystematics, or systems biology, recognizes the redundancies and uncertainties that separate the genotype (molecular profiling) from the phenotype (functional analyses) are not trivial. Our laboratory conducts phenotype analyses. Caris conducts genotype analyses.

Cancers produce novel proteins that can suggest, though not diagnose, a source of the tumor. The original blood tests included CEA, known to occur in many adenocarcinomas including lung, gastrointestinal and breast. CA 27-29 and CA15-3 have been most closely associated with breast cancers. CA 125 is the marker for ovarian as is HE4, a more recently developed test. PSA and prostatic acid phosphatase are used in prostate cancer. CA 19-9 is associated with pancreatic cancer. Germ cell tumors can produce B-HCG and AFP. AFP is also associated with hepatocellular cancer. Despite all of this, some tumors express no markers while other tumors express markers not generally associated with that disease type. This is part of the reason why markers are not promoted for general use at academic centers. Cancers produce novel proteins that can suggest, though not diagnose, a source of the tumor. The original blood tests included CEA, known to occur in many adenocarcinomas including lung, gastrointestinal and breast. CA 27-29 and CA15-3 have been most closely associated with breast cancers. CA 125 is the marker for ovarian as is HE4, a more recently developed test. PSA and prostatic acid phosphatase are used in prostate cancer. CA 19-9 is associated with pancreatic cancer. Germ cell tumors can produce B-HCG and AFP. AFP is also associated with hepatocellular cancer. Despite all of this, some tumors express no markers while other tumors express markers not generally associated with that disease type. This is part of the reason why markers are not promoted for general use at academic centers.

This is a very controversial topics. Triple negative breast cancer does not mean automatically chemotherapy. The very very small tumors with no lymph node many not have an indication of chemotherapy depending on the patient's general health condition or age. So question is what is small small? This is where split opinions do exist. This is something that we can not truly discuss unless we see each case in the clinic. This is a very controversial topics. Triple negative breast cancer does not mean automatically chemotherapy. The very very small tumors with no lymph node many not have an indication of chemotherapy depending on the patient's general health condition or age. So question is what is small small? This is where split opinions do exist. This is something that we can not truly discuss unless we see each case in the clinic.

THank you!It did not miss the tumor. The mammography I had in September 2009 saw the tumor. Ironically September 2009 was the month that I was scheduled anyway for my annual mammo as the previous one was in September 2008. But because we discovered the lump at the very end of August 2009, it turned into a diagnostic mammo.I did go back and reqest the x-ray and the mammo report again from the mammo in 2008, and had my current radiologist take a look at it. Although I had dense breasts, nothing was there at that time. I had just had an annual GYN check up in early July 2009, which included a routine breast exam. Again, my breasts were cystic and dense, but no tumor was felt that day. I have many questions that can't be answered. Was it there and they missed it? Did I miss it? Did it grow that fast that soon? I hear with Triple Negative anything is possible. Those words "dense" and "cystic" never worried me before, but if my daughters have the same body type, I will for sure encourage them to be aware, be healthy, avoid carcinogens and most important, do frequent breast exams. We need to know our girls! THank you!It did not miss the tumor. The mammography I had in September 2009 saw the tumor. Ironically September 2009 was the month that I was scheduled anyway for my annual mammo as the previous one was in September 2008. But because we discovered the lump at the very end of August 2009, it turned into a diagnostic mammo.I did go back and reqest the x-ray and the mammo report again from the mammo in 2008, and had my current radiologist take a look at it. Although I had dense breasts, nothing was there at that time. I had just had an annual GYN check up in early July 2009, which included a routine breast exam. Again, my breasts were cystic and dense, but no tumor was felt that day. I have many questions that can't be answered. Was it there and they missed it? Did I miss it? Did it grow that fast that soon? I hear with Triple Negative anything is possible. Those words "dense" and "cystic" never worried me before, but if my daughters have the same body type, I will for sure encourage them to be aware, be healthy, avoid carcinogens and most important, do frequent breast exams. We need to know our girls!

Location does matter. Firstly, it can affect how the biopsy is done. Generally, image-guided needle biopsy is the method of choice, however, if the lesion is too superficial, near the skin, needle biopsy may not be possible. In that case excisional biopsy may be preferred. Similarly, in patients who have had augmentation mammoplasty, if the lesion is too close to the implant, excisional biopsy may be less likely to damage the implant.
With regard to lumpectomy for breast cancer, location of the tumor will influence incision placement. Oncoplastic techniques should be employed such as placing incisions along lines of skin tension (marked with the patient sitting up or standing), mobilizing breast tissue to close the dead space, and using cosmetic skin closure.
When tumors are behind the areola, resection of the nipple and areolar complex may be necessary to obtain clear margins. The breast will lose some projection, but the majority of the breast mound can be preserved. Location does matter. Firstly, it can affect how the biopsy is done. Generally, image-guided needle biopsy is the method of choice, however, if the lesion is too superficial, near the skin, needle biopsy may not be possible. In that case excisional biopsy may be preferred. Similarly, in patients who have had augmentation mammoplasty, if the lesion is too close to the implant, excisional biopsy may be less likely to damage the implant.
With regard to lumpectomy for breast cancer, location of the tumor will influence incision placement. Oncoplastic techniques should be employed such as placing incisions along lines of skin tension (marked with the patient sitting up or standing), mobilizing breast tissue to close the dead space, and using cosmetic skin closure.
When tumors are behind the areola, resection of the nipple and areolar complex may be necessary to obtain clear margins. The breast will lose some projection, but the majority of the breast mound can be preserved.

This will completely depend on the type of tumor. Some of the more aggressive cancers actually respond best to chemotherapy as neoadjuvant treatment, while some of the less aggressive tumors may respond better to anti-estrogen therapy (tamoxifen or an aromatase inhibitor). Tumors that over-express Her2/neu will often respond best to a combination of chemotherapy and herceptin. Newer molecular profiling tests that are done on the breast cancer (MammaPrint and Oncotype Dx) can give us some very helpful information regarding the aggressiveness of a cancer as well as the potential for response to different therapies. Each case is really individualized, and we are now more than ever better able to tailor a particular regimen to a patient's individual cancer for the best results. This will completely depend on the type of tumor. Some of the more aggressive cancers actually respond best to chemotherapy as neoadjuvant treatment, while some of the less aggressive tumors may respond better to anti-estrogen therapy (tamoxifen or an aromatase inhibitor). Tumors that over-express Her2/neu will often respond best to a combination of chemotherapy and herceptin. Newer molecular profiling tests that are done on the breast cancer (MammaPrint and Oncotype Dx) can give us some very helpful information regarding the aggressiveness of a cancer as well as the potential for response to different therapies. Each case is really individualized, and we are now more than ever better able to tailor a particular regimen to a patient's individual cancer for the best results.