What This Means For You
If youve been diagnosed with triple-negative breast cancer, this study offers some encouraging and interesting information. The results strongly suggest that triple-negative breast cancers are not all the same and that certain subtypes have better survival rates than hormone-receptor-positive breast cancer.
Determining the subtype of triple-negative breast cancer is not universally done. Still, many cancer centers do this type of testing. You may want to ask your doctor about this study, as well as whether subtype testing has been done as part of your pathology report and what it means for your prognosis and treatment.
Armed with the most complete information you can get, you and your doctor can make the best decisions for your unique situation.
Tumour Distribution And Clinical Strategies
MF/MC breast cancer is divided into MF breast cancer and MC breast cancer according to the location of tumours. However, there are no data to confirm whether there are differences in biological behaviours and prognoses between MF and MC breast cancers. Rosencranz noted that MC breast cancer may be associated with a low OS, while MF breast cancer does not affect the OS. Lynch et al. found that both MF breast cancer and MC breast cancer were associated with earlier onset age, higher tumour stage and higher lymph node stage. Therefore, more follow-up data are needed to clarify whether there are differences in the choice of surgical methods for MF breast cancer and MC breast cancer and whether BCT will have different effects on the prognosis of these patients. Currently, most studies believe that BCT is suitable for patients with limited distribution of early- and middle-stage MF/MC breast cancer. BCT is not recommended for patients with diffuse ductal carcinoma in situ because it is difficult to obtain a negative margin.
Posh Study Brca1/2 Cohort
There were 338 germline BRCA mutation carriers in the POSH study breast cancer cohort focality data was missing in 37 cases, leaving 180 women with a BRCA1 mutation and 121 with a BRCA2 mutation for analysis. There were 81 diagnoses of MF/MC disease and 220 diagnoses of unifocal disease. Clinicopathological findings in the POSH cohort are detailed in Table 2. Mean age of diagnosis was 34 years, with no difference seen in the age at diagnosis for MF/MC tumours versus unifocal tumours . MF/MC breast cancer was identified in 26.9% of BRCA1/2 mutation carriers who developed breast cancer. Prevalence of MF/MC disease was 13.3% amongst BRCA1 mutation carriers diagnosed with breast cancer, and 47.1% amongst BRCA2 mutation carriers diagnosed with breast cancer. Therefore, prevalence of MF/MC disease in BRCA2 mutation carriers was 3.5-fold greater than in BRCA1 mutation carriers in this independent cohort of BRCA1/2 carriers .
The unadjusted odds of a breast cancer being MF/MC in BRCA2 mutation carriers was 5.8 times greater than in a BRCA1 mutation carrier who developed breast cancer . Adjustment for oestrogen receptor status gave odds of a BRCA2 mutation carrier developing MF/MC breast cancer 4.2 times greater than a BRCA1 mutation carrier . A similar reduction in the magnitude of the odds ratio was observed in our dataset when analysis was adjusted for oestrogen receptor status.
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Characteristics Of Eligible Studies
Of the 468 studies identified initially, 41 full-text articles were retrieved based on the dedicated evaluation. Finally, 10 studies with 19,272 patients were enrolled, of whom 1,616 were diagnosed with MF/MC breast cancer and 17,656 were diagnosed with unifocal breast cancer. The year of publication ranged from 1989 to 2015. The sample size of the included studies ranged from 55 to 11,983 patients. The characteristics of the 10 eligible studies are summarized in Table 1. The PRISMA statements of search results are presented in Figure 1.
Flow diagram of search strategy and included studies.
The cumulative LR was 5.6% for MF/MC disease treated with BCT, 4.2% for unifocal disease treated with BCT, and 2.0% for MF/MC disease treated with mastectomy.
How Is It Treated
Your treatment will depend on the stage of your cancer. If the cancer is early stage meaning the tumors are only in one quadrant of your breast breast-conserving surgery is possible. This procedure removes as much of the cancer as possible, while preserving the healthy breast tissue around it.
Large tumors or cancers that have spread may require mastectomy surgery to remove the whole breast. Lymph nodes may also be removed during the surgery.
Although breast cancer treatments can improve your survival odds, they can have side effects.
Side effects from breast-conserving surgery include:
- pain in the breast
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Limitations And Future Guidelines
The incidence of MF/MC breast cancer varies between 6 and 7%, depending on somewhat arbitrary definition of the MF/MC imaging method sensitivity and biopsy performed by the pathologist. The TNM stage does not include multifocality in the tumour classification . As further progress is made in the pre-operative diagnostics, the number of identified MF and MC tumour is increasing . and consequently better manuals are required for treating them , as well as standardised immunohistochemical procedures which would reduce the subjectivity and intralaboratory variations in the interpretation .
Future studies observing molecular profiles of separate tumour foci in the same breast could shed light on this matter and provide clinically relevant information for therapy manual-based decisions. Another limitation is the median monitoring of under 5 years and the bias of multicentric studies . Failure to factor in the heterogeneity of the focus of an additional tumour could prevent the patients from taking advantage of appropriate therapies . Most studies are retrospective or incidental in nature, which neither compare breast-conserving surgery with mastectomy nor analyse locoregional recurrence as a primary goal in MSIBC .
What Kinds Of Support Are Available
If youve recently been diagnosed with multifocal breast cancer, you might have a lot of questions about everything from your treatment options to how much theyll cost. Your doctor and the rest of your medical team can be good sources for this information.
You can also find more information and support groups in your area through cancer organizations like these:
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Multifocal Vs Multicentric Breast Cancer
According to the National Cancer Institute more than 192,000 American women are diagnosed with breast cancer each year. Breast cancer can occur in both men and women. Even though male breast cancer is rare, the National Cancer Institute estimates that about 1,900 men are diagnosed with breast cancer each year. Determining whether your breast cancer is multifocal or multicentric will influence your treatment plan.
Breast cancer is the out-of-control growth of cells in your breast. These cells clump together to form tumors that can grow and invade your normal tissue. Breast cancer can form in any part of your breast. Not all tumors or lumps are cancer. Tumors are considered cancerous if they are found to be malignant. Malignant tumors cause damage to surrounding normal tissue. Noncancerous, or benign, tumors may still need to be treated if they are causing discomfort. There is no known cause of breast cancer.
Multifocal Breast Cancer
Multifocal breast cancer occurs when there are multiple tumors in your breast that all come from one original tumor. Parts of the original tumor break off and start to grow separately from the original. These tumors tend to be located in the same section of the breast. Multifocal breast cancer tends to be a less invasive cancer because the tumors have not moved into other parts of the body.
Multicentric Breast Cancer
What Is Multifocal Breast Cancer
A person who has received a diagnosis of multifocal breast cancer has more than one invasive tumor in one area of their breast.
Experts classify breast cancers into different categories, depending on their characteristics. A person can receive one of the following diagnoses:
- Unifocal breast cancer, where there is only one tumor in the breast.
- Multifocal breast cancer, when at least two invasive tumors develop in the same quadrant, or area, of the breast. All tumors arise from one original tumor.
- Multicentric breast cancer, where at least two tumors develop separately, often in different areas of the breast.
Multifocal breast cancer is not necessarily more advanced or aggressive than single tumor breast cancer. Staging multifocal breast cancer depends primarily upon the characteristics of the primary, or largest, tumor.
However, there is more risk of larger tumors or cancer spreading to the lymph nodes, so that the prognosis may be less favorable for some people with multifocal compared with unifocal breast cancer.
Staging for multifocal breast cancer varies with doctors basing this on the characteristics of the primary tumor and whether or not cancer is present in other areas of the body. Treatment plans and long-term outlook depend on the cancer stage.
There are five stages, starting from zero, that indicate if, and how far, a tumor has spread.
The TNM system does not include whether a tumor is multifocal or unifocal.
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Contralateral Breast Cancer Screening And Sensibility
Contralateral mammography is a mandatory follow-up for all patients with breast cancer. If multifocal or multicentric breast cancer is truly present, mammography examinations arent always able to detect it, in fact, the sensitivity for detecting this situation with mammography is between 15% to 45%, which is not entirely satisfactory. This sensitivity rate is increased to between 48% and 62% with the addition of whole-breast sonography, but magnetic resonance imaging is the most sensitive screening tool, with a detection rate of around 81%.
The sensitivity of mammography in detecting multifocal breast tumors increases in women with a fatty pattern of breast density. In women with dense breast, the sensitivity of mammography in detecting multifocal breast tumors droms by about 10%.
Breast Magnetic Resonance Imaging Of Multicentric Multifocal And Bilateral Cancer A Case
European Oncology & Haematology,
Multifocal or multicentric breast cancer can be difficult to detect on mammography or ultrasound, particularly in patients with dense breast tissue. A multimodality approach that includes breast magnetic resonance imaging is indicated, particularly when conservative surgery is being considered as it is the most sensitive technique for identifying additional sites of disease. However, its influence on recurrence and survival rates has yet not been clearly established, and false-positive cases may lead to more aggressive management and treatment. Radiologists should therefore be aware of relevant breast MRI findings. Infiltrating carcinomas, contralateral unsuspected carcinomas, occult carcinomas, false-positive cases and post-chemotherapy changes. Several cases of multiple-site breast carcinomas and their corresponding mammographic, ultrasound and MRI features have been reviewed for this article, in which the definition and differences between multifocal, multicentric and contralateral breast carcinoma are explained and the most relevant imaging findings on MRI are illustrated and correlated with mammogram and ultrasound findings. Finally, the role of breast MRI in the pre-operative assessment of breast cancer is discussed.
The authors have no conflicts of interest to declare.
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Epidemiology And Risk Factors
Based on data from the literature, there is no consensus on the factors relating to the development of multicentric carcinomas . MF/MC BC incidence ranges from 6 to 77% . Bilateral breast cancers are responsible for 2 to 6% of all breast carcinomas . Earlier studies have shown that one of the most important risk factors for MCBC is if the first occurrence is an invasive lobular carcinoma . Low-grade invasive ductal carcinomas are not linked with the number of tumour masses in the contralateral breast. All of these observations contradict the fact that ILC is more common among patients with bilateral and multifocal BC solely due to slower growth rates .
There are no differences when it comes to patient age, tumour stage, or the presence of multifocal, multicentric, and bilateral ILCs . Contralateral tumour incidence, in particular synchronous ILCs, is in the 5 to 19% range, which is more than invasive ductal carcinoma of no special type . BSBC is a rare entity with an incidence between 1 and 3%. Surprisingly, there has not been an increase in the BSBC incidence since 1980. A lower incidence of metachronous bilateral breast cancer was observed, likely due to the introduction of systemic adjuvant therapy. In the study on incidence of bilateral breast cancers in Sweden, conducted by Hartman and co-authors reported that the incidence of BSBC was approximately 100 times greater than what can be explained as coincidence or a cumulative effect of exogenous carcinogens ,
Features Of Multifocal Invasive Breast Carcinomas
A total of 246 cases of ipsilaterally multifocal invasive breast carcinoma were included in the analysis. The main characteristics of these cases are summarized in . Of all cases, 198 had 2 foci, 33 had 3 foci, and 15 had 4 or more foci of invasive tumor. In cases with more than 2 foci, not every focus was necessarily tested for HER2. Our selection criteria identified all cases in which 2 tumor foci were present, and both tumor foci were tested. Depending on referring requests, a varying selection of blocks was tested in cases with 3 or more tumor foci. Overall, 2 blocks were tested in 219 cases, 3 blocks in 20 cases, and 4 or more in 7 cases. In some cases , testing of the additional focus or foci would be recommended under the CAP Cancer Protocl. The reason for testing in the remaining cases was unknown .
Characteristics, Including HER2 Results, of 246 Multifocal Breast Carcinoma Cases in Which More Than 1 Block Was Tested for HER2a
A subset of the cases was referred for confirmatory HER2 testing only. As such, hormone receptor status was available for 211 of 246 cases. Of these 211 cases, estrogen receptor was positive in at least 1 focus in 180 , low positive in 4 , and negative in 27 . Of the 211 cases, progesterone receptor was positive in 154 , low positive in 11 , and negative in 46 . Overall, ER and PR results were concordant between foci in 205 of 211 cases. Three of the 6 discordant cases also showed discordant HER2 results between tumor foci .
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Multifocal Staging: Increased Risk Of Axillary Metastasis
The discovery of multifocal and multicentric breast cancer presents new challenges in terms of staging, follow-up procedures, and treatments. Of the approximately 11% of patients who have developed multifocal and multicentric tumors, approximately 52% of these will also present with axillary lymph node involvement. By contrast, axillary node involvement is discovered with unifocal breast cancers only about 38% of the time. This suggests that women with multifocal breast carcinomas have an increased tumor load, or a more serious and aggressive kind of breast cancer. Multifocal and multicentric tumors have tended to be understaged, often leading to a false sense of assurance and denying the patient the opportunity to aggressively pursue adjuvant therapies.
How Common Is It
As a result of differences in definitions and diagnostic techniques, anywhere from 4 to 75 percent of breast tumors are multifocal or multicentric.
One study involving 1,158 people with breast cancer of stages 1, 2, and 3 found multifocal breast cancer in 131 of the participants, or 11.3 percent. They found multicentric breast cancer in 60 cases, or 5.2 percent of participants.
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Other Classifications Of Breast Cancer
Doctors classify different types of breast cancers based on the type of cells in which cancer develops. Most breast cancers are carcinomas, which means they grow in the cells that line the organs and body tissues.
Breast cancer is either invasive or noninvasive:
- Noninvasive breast cancers develop inside the milk-producing glands, or lobules, or inside the milk ducts and do not spread outside these areas.
- Invasive breast cancers grow beyond the lobules or ducts and spread into other areas of the breast or parts of the body.
The main types of breast cancer include the following:
Molecular And Genetic Testing
It is not clear whether multifocal/multicentric BCs with different phenotypes are of independent origin due to the fact that phenotypic changes may occur during the tumour progression and dissemination . A few studies, using various molecular methods, showed that bilateral breast cancers are most likely not genetically identical . While the presence of a different phenotype is a clear indicator of separate synchronous primary tumours, over 70% of invasive BCs classified as IDC have identical morphology, meaning that the tumours are clonally related. Using targeted gene sequencing in patients with multiple invasive ductal carcinomas of the same grade and hormone receptor status, it was determined that one third of the cases shows identical mutation profile, one third shares mutations with individual mutations in different foci suggesting identical clonal origin, and one third exhibits no common mutations. Despite common mutations not being present, common changes in copies among the lesions were found, which requires more detailed examinations with methods such as sequencing the entire genome, which would reveal common subclones with a clonal distinction in a larger number of cases .
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Multifocal Breast Cancer In Young Women With Prolonged Contact Between Their Breasts And Their Cellular Phones
Nimmi S. Kapoor
1Breastlink, Department of Surgery, 230 S. Main Street, Suite 100, Orange, CA 92868, USA
2Department of Pathology, St. Joseph Hospital, University of California Irvine, 1100 West Stewart Drive, Orange, CA 92868-5600, USA
3Breastlink, Department of Radiology, 230 S. Main Street, Suite 100, Orange, CA 92868, USA
4Bay Area Breast Surgeons, Inc., Department of Surgery, 3300 Webster Street, Suite 212, Oakland, CA 94609, USA
5Department of Obstetrics and Gynecology, Rational Therapeutics, University of California Irvine, Long Beach, CA, USA
1. Case Reports
1.1. Case 1
A 21-year-old female presented with left spontaneous bloody nipple discharge. Her history was notable for keeping her cellular phone tucked into her bra on the left side for several hours each day. Her mammogram showed extensive pleomorphic calcifications and densities from the retroareolar region to the chest wall spanning a length of 12cm. A magnetic resonance image showed extensive abnormal nonmass enhancement in a segmental distribution corresponding to changes seen on her mammogram 1). She was treated with mastectomy and pathology revealed extensive ductal carcinoma in situ with multifocal microinvasion. Sentinel lymph nodes were negative for metastatic disease.
1.2. Case 2
1.3. Case 3
1.4. Case 4