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Lobular Vs Ductal Breast Cancer

Multivariate Analysis Of Luminal Type

Invasive Ductal and Lobular Breast Cancer, Is a Combination Possible?

Multivariate analysis was performed using Cox regression models to determine the independent prognostic factors of luminal type breast cancer. Factors in this analysis were pathological type , age, tumor size, lymph node status, histological grade, endocrine therapy, and chemotherapy. Pathological type, tumor size, lymph node status, histological grade, and endocrine therapy were prognostic factors independently associated with recurrence of luminal type breast cancer . Moreover, tumor size and lymph node status were the prognostic factors for better survival in luminal type breast cancer.

Table 4 Multivariate analysis for luminal types

Hierarchical Clustering Of Lobular Tumors

Seventeen lobular and 6 reduction mammoplasty samples were analyzed by hierarchical clustering on a subset of 3500 genes to explore tumor grouping and gene clustering in the lobular samples. These genes were chosen on the basis of being present in at least 80% of the lobular and normal cases.

Several clusters of related genes were evident by hierarchical clustering, the largest of which was related to proliferation . This cluster included genes such as cyclin E1, cdc6, PCNA, B-myb, histones and histone related centromeric proteins , the chek1 mitotic checkpoint gene, and GART . Three groups of tumors were evident. Group I, which included the normal samples, was characterized by low levels of expression of genes in the proliferation-associated cluster, group II tumors showed the highest levels of expression, and group III showed mixed expression levels.

A cluster including matrix metalloproteinase MMP2 and its inhibitor, TIMP2, was also evident. Expression of genes in this cluster were highest in tumors from group I, with low levels of expression in group II tumors, and low levels in most tumors in group III.

Tumors with different stages, grades, nodal status, and outcomes were found in every group, indicating that tumor clustering was not driven by clinical parameters. Two of the lobular cases were progesterone receptor negative by immunohistochemistry, and both were found in the group I cluster that showed low levels of proliferation.

Symptoms Of Invasive Lobular Carcinoma

In many cases, invasive lobular carcinoma causes no symptoms and is found after your doctor sees a suspicious area on a screening mammogram.

In other cases, you or your doctor may feel a thick or swollen area in your breast. ILC is less likely than other breast cancers to cause a hard lump. Any of the following unusual changes in the breast can be a first sign of invasive lobular carcinoma:

  • determine if certain clinical trials may be a good option for you

Generally, the stage of invasive lobular carcinoma is described as a number on a scale of I through IV. Stages I, II, and III describe early-stage cancers and stage IV describes cancers that have spread outside the breast to other parts of the body, such as the bones or liver.

Once a diagnosis of invasive lobular carcinoma has been made, your doctor will do more testing to collect information on the characteristics of the cancer. These tests, as well as the results of your biopsy, make up the parts of your pathology report.

Information commonly collected as part of a pathology report include:

Treatments for invasive lobular carcinoma may include:

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What Are The Adjuvant Treatments For Invasive Lobular Breast Cancer

After surgery you may need further treatment. This is called adjuvant therapy and can include:

The aim of these treatments is to reduce the risk of breast cancer cells returning in the same breast or developing in the other breast, or spreading somewhere else in the body.

Which treatment you have will depend on your individual situation.

Some of these treatments are given before surgery. This is known as neo-adjuvant or primary therapy.

Identification Of Differentially Expressed Genes

Breast Carcinoma in Situ

Gene expression data from The Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium were downloaded from the Gene expression Omnibus database and Synapse software platform respectively.

TCGA tumors were assigned to one of the five intrinsic subtypes based on PAM50 similarly as described in Curtis 2012. Briefly, we first created an ER balanced sub-samples by combining all ER- tumors and the same number of ER+ tumors randomly drawn from TCGA. Log2 transcripts per million of all tumors were then median centered by extracting the median calculated from ER balanced sub-samples. Genefu R package was used to assign intrinsic subtypes for all tumors using median centered data. We repeated drawing ER balanced samples 100 times, and the most frequently assigned subtypes were use as final subtypes.

Since the number of TCGA cases decreased slightly , we repeated the DE analysis with altered numbers . This analysis confirmed that changes in DE genes and pathways were not caused by change in numbers of tumor samples . In figures with the GSVA or immune phenotype data from Tamborero et al. , all of their 924 tumors were used . All other analyses with TCGA used the complete set of tumors .

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Environmental And Lifestyle Risk Factors

Most breast cancers are related to female hormones, and therefore any factor that increases exposure to these hormones is a potential risk factor. In particular, reproductive factors associated with increased exposure to endogenous estrogens produced by the ovaries, such as earlier menarche, late menopause, low parity, and late age at first birth, are recognized breast cancer risk factors . Similarly, women exposed to exogenous hormones are often at increased risk .

Lifestyle factors are also associated with breast cancer. There is an estimated 10% increase in risk per 10 g of ethanol consumed every day . Being overweight or obese is also associated with breast cancer risk, but only in postmenopausal women, with a gain of 5 kg/m2 in body mass index resulting in an 8% increase in disease risk . On the contrary, excess weight is associated with a decrease in risk in premenopausal women. Again, these associations can be explained by hormonal factors: alcohol consumption and postmenopausal obesity are related to higher circulating estrogen levels . In postmenopause, elevated estrogen levels are most probably due to extraglandular production in the adipose tissue, whereas in premenopause, the decrease in female hormone synthesis associated with anovulatory cycles in obese women likely explains the inverse association with breast cancer .

Current And Future Research

The most important finding from this analysis is the mounting evidence that we need to pay attention to late recurrences for ILC patients. The registry also includes important data on patterns of recurrence, and we intend to dive deeper into metastatic patterns and survival outcomes, says Dr. Kruse.

This study is the first of many planned which are enabled by the volume of patients and close collaboration among the institutions of the Great Lakes Breast Cancer Consortium.

Our next steps are to look at the type of treatments patients received: who got chemotherapy, who didnt and how they responded, says Dr. Kruse. We would also love to be able to look at the types of endocrine treatment received along with the duration of treatment. This is a very relevant clinical question that is unlikely to be able to be answered in a prospective trial.

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Patient And Tumor Characteristics

We identified 1,998 cases of IDC and 115 cases of ILC after excluding patients according to the criteria described above as well as cases of carcinoma in situ. Among these, the number of cases of IDC and ILC with luminal subtype were 1,661 and 104, respectively. Among ILC, 3 % were hormone receptor positive and HER2 positive and 2 % were hormone receptor negative and HER2 positive, and 5 % were triple negative. The median follow-up time was 64 months . The clinical and pathological tumor characteristics of luminal IDC and luminal ILC are shown in Table . The tumor size of luminal ILC was larger than that of luminal IDC . Luminal ILC was more likely to have a lower histological grade than luminal IDC .

Table 1 Patient characteristics

Positive margins were more frequently found in luminal ILC than in luminal IDC . The majority of patients with luminal ILC were treated with adjuvant hormonal therapy. In addition, those with luminal ILC were more likely to receive adjuvant hormonal therapy than those with luminal IDC . However, there were no significant differences in other characteristics between the two groups.

Treating Invasive Breast Cancer

Dr. Shih on Treating Lobular vs Ductal Breast Cancers

Treatment of invasive breast cancer depends on how advanced the cancer is and other factors. Most women will have some type of surgery to remove the tumor. Depending on the type of breast cancer and how advanced it is, you might need other types of treatment as well, either before or after surgery, or sometimes both.

See Treating Breast Cancer for details on different types of treatment, as well as common treatment approaches based on the stage or other factors.

Our team is made up of doctors and oncology certified nurses with deep knowledge of cancer care as well as journalists, editors, and translators with extensive experience in medical writing.

Arpino G, Infiltrating lobular carcinoma of the breast:tumor board characteristics and clinical outcome. Breast Cancer Research. 2004 6: 149.

Dillon DA, Guidi AJ, Schnitt SJ. Ch. 25: Pathology of invasive breast cancer. In: Harris JR, Lippman ME, Morrow M, Osborne CK, eds. Diseases of the Breast. 5th ed. Philadelphia, Pa: Lippincott-Williams & Wilkins 2014.

Henry NL, Shah PD, Haider I, Freer PE, Jagsi R, Sabel MS. Chapter 88: Cancer of the Breast. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloffs Clinical Oncology. 6th ed. Philadelphia, Pa: Elsevier 2020.

Huober J, Gelber S, Goldhirsch A, et al. Prognosis of medullary breast cancer: analysis of 13 International Breast Cancer Study Group trials. Ann Oncol. 2012 23:28432851.

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Lobular And Hormone Therapy

Fred Hutch has long been associated with lobular research.

In the late 1990s, Hutch epidemiologists began investigating the possibility that lobular breast cancer was on the rise. Then in 2000, Dr. Christopher Li and colleagues published a study showing that it was â and its rise was somehow linked with menopause. A landmark Womenâs Health Initiative study filled in the rest of the puzzle two years later: the rise in lobular breast cancer was directly linked to the use of combined hormone therapy, or CHT, by postmenopausal women.

Unfortunately, the lobular association seemed to get lost in all the brouhaha about CHT increasing the risk of breast cancer.

âPeople often seem to get this wrong,â said Porter of the 2002 WHI finding. âItâs not that breast cancer, in general, is increased by hormone replacement therapy. Lobular breast cancer is increased by taking combined estrogen and progestin hormone replacement therapy. Something in that combination is creating a situation where lobular cancer is more likely to develop.â

The discovery turned out to be a mixed blessing for lobular cancer research. On the plus side, it curbed the use of CHT and the rates of lobular cancer fell. On the downside, it triggered a drop in ILC research funding.

Premenopausal breast cancer patients like Pate, who never took combined hormone therapy, feel the lobular code is far from cracked. Researchers, too, believe thereâs much more to be done.

Pathological Assessment And Definition Of Molecular Subtypes

Histopathological diagnoses of ILC and IDC using hematoxylineosin staining were made by several pathologists at Aichi Cancer Center Hospital. Hormone receptor status was determined by immunohistochemical staining. Hormone receptor-positive status was defined as a score of equal or greater than 3 of ER on the Allred Score . HER2 positive was defined as a Herceptest-score of 3+ or fluorescent in situ hybridization positive following a Herceptest-score of 2+. The definition of luminal type was determined as ER positive and HER2 negative. Histological grading was performed using the Nottingham histological grading system. Tumor stage was stratified according to the AJCC 7th edition TNM staging system for breast cancer. The dataset supporting the conclusions of this article is included within the article and its additional file .

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Univariate Analysis Of Luminal Type

The prognosis of luminal ILC was significantly worse than that of luminal IDC. The 5-year DFS was 91.9 % and 88.4 % for patients with luminal IDC and luminal ILC, respectively , while the 5-year OS was 97.6 % and 93.1 %, respectively, for patients with luminal IDC and luminal ILC .

Fig. 1

Patient outcomes of luminal IDC and luminal ILC disease-free survival overall survival, IDC invasive ductal carcinoma, ILC invasive lobular carcinoma

The survival curves for luminal IDC and luminal ILC after stratification by tumor size are shown in Fig. . There were no significant differences in DFS between the two groups However, the 5-year DFS of luminal ILC tended to be worse than that of luminal IDC in cases with large tumors . The survival curves for luminal IDC and luminal ILC after stratification by lymph node status are shown in Fig. . There were no significant differences in DFS between the two groups in the node negative population . However, the 5-year DFS of luminal ILC was significantly worse than that of luminal IDC in the node positive population . Furthermore, the 5-year OS of luminal ILC was also significantly worse than that of luminal IDC in the node-positive population .

Fig. 2

Patient outcomes of luminal IDC and luminal ILC stratified according to tumor size T1 T2 T3, IDC invasive ductal carcinoma, ILC invasive lobular carcinoma

Fig. 3Table 2 Univariate analysis for luminal types Fig. 4

Survivorship Care After Invasive Lobular Carcinoma Treatment

Mammary Irony: T1cN0M0

Because of better diagnostic tests and advances in cancer treatments, more people are living longer than ever after being diagnosed with any type of cancer, including breast cancer. Experts estimate that there are more than 3.8 million breast cancer survivors in the United States.

Still, because of treatments theyve received, many breast cancer survivors have a higher risk of developing other diseases as they age, including high blood pressure, heart disease, and osteoporosis. To make sure breast cancer survivors are regularly screened for these and other diseases, experts have developed the idea of survivorship care planning.

Survivorship care plans are written documents made up of two parts.

The first part is a treatment summary, a record of all the breast cancer treatments youve received.

The second part is basically a roadmap of what you can expect in the years after treatment, including any late or long-term side effects you might have, and a schedule of how youll be monitored for these side effects and other health conditions. This part of the survivorship care plan usually includes:

  • the tests youll have

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    which doctors will order the tests

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    a schedule of when the tests will be done

  • resources, if you need more information

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Great Lakes Breast Cancer Consortium

Lobular breast cancer is the second most common type of breast cancer from a histological perspective, but it only represents about 10 to 15 percent of breast cancer cases. Because of its rareness, oncologists have tended to view it and treat it in the same way as the more common ductal breast cancer.

But as more research is performed on lobular cancers, investigators are starting to recognize that it has some distinct features apart from ductal cancer, especially with respect to how it metastasizes and its decreased sensitivity to chemotherapy.

With this in mind, scientists from Cleveland Clinic, University of Pittsburgh Medical Center and Ohio State University have created a lobular breast cancer registry that will include cases from 1990 to the present. The present study is one of the first from this newly created registry.

Where Is Lobular Breast Cancer Likely To Spread

What Is Invasive Lobular Breast Cancer? Invasive breast cancer that begins in the lobules of the breast and spreads to surrounding normal tissue. It can also spread through the blood and lymph systems to other parts of the body. Invasive lobular breast cancer is the second most common type of breast cancer. Over 10% of invasive breast cancers are invasive lobular carcinomas.

What is life expectancy with metastatic breast cancer?

Life expectancy statistics for metastatic breast cancer are not high, as this is the most advanced stage of breast cancer. The expansion of cancer and resulting symptoms vary from person to person. However, available treatments may help a patient feel more comfortable and live longer.

What are the four types of breast cancer?

Carcinoma. It is the most common form of cancer that affects the epithelial cells which form the lining of internal organs or the skin.

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Symptoms Of Lobular Breast Cancer

Lobular breast cancer sometimes begins without symptoms. It may show as an abnormal area on a mammogram, which leads to further examination.

Spotting ILC on a mammogram can be difficult because the cancer cells spread in a line rather than in a distinctive lump, as in IDC. Magnetic resonance imaging imaging is reported to provide more sensitive images that may show the cancer better.

The first symptom of ILC is sometimes a thickening or hardening of a portion of the breast. This thickening can be felt by touch, but it feels different from the classic lump associated with IDC, the more common breast cancer.

Other symptoms of ILC may include:

  • swelling or fullness in a part of the breast, or in the whole breast
  • a change in the skin texture in a part of the breast
  • dimpling in the breast

The exact cause of ILC is currently unknown. But there are some risk factors that are associated with ILC. These can include:

  • taking hormone replacements, for menopause for example

Although people can be diagnosed with lobular breast cancer at any age, its most common in women ages 55 years and older. Research suggests that hormone replacement therapy after menopause, especially with progesterone, may increase the risk of this type of cancer.

Magnitude Of Benefit From Use Of Trastuzumab

Lobular Vs Ductal Breast Cancer

Overexpression or amplification of the HER2 gene occurs in 35% of classic ILC . Furthermore, a number of studies suggest that patients with ILC variants, such as mixed-nonclassic ILC, have higher rates of HER2 positivity . Despite HER2 positivity being an independent prognostic factor associated with worse survival outcomes for patients diagnosed with ILC , few available data describe the magnitude of benefit of anti-HER2 therapies in this particular subtype.

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