Registry Study of Pregnancy and Breast Cancer

Data for this study will be recorded into the electronic case report form (eCRF) via web using Remote Data Capture (RDC) from Oracle Clinical®. Once patient has signed the ICF or verified that the data of deceased patients can be included, designated site personnel will complete the register of each patient in the eCRF, where an identification number will automatically be assigned.

Data will be recorded in the eCRF at the time of patient enrollment and approximately every year.

Data for this study will be recorded into the eCRF via web using RDC (Remote Data Capture) from Oracle Clinical®. Once patient has signed the ICF or verified that the data of deceased patients can be included, designated site personnel will complete the register of each patient in the eCRF, where an identification number will automatically be assigned.

Data will be recorded in the eCRF at the time of patient enrollment and approximately every year.

Data for this study will be recorded into the eCRF via web using RDC (Remote Data Capture) from Oracle Clinical®. Once patient has signed the ICF or verified that the data of deceased patients can be included, designated site personnel will complete the register of each patient in the eCRF, where an identification number will automatically be assigned.

Data will be recorded in the eCRF at the time of patient enrollment and approximately every year.

Assess the clinicopathological characteristics of cancer in the patients enrolled in the study. For this, it is used the Tumor, Node, Metastasis (TNM) staging system is the most common way that doctors stage breast cancer. Patient scans and tests give some information about the stage of the cancer.

Tumor (T) size describes the size of the tumour. Larger T is associated with inferior survival.

Tumor cannot be assessed (TX): can't be assessed. Tis: ductal carcinoma in situ. T1: tumour is 2 centimetres (cm) across or less. T1mi: tumour is 0.1cm across or less T1a: tumour >0.1 cm but <0.5 cm T1b: tumour >0.5 cm but <1 cm T1c: tumour >1 cm but <2 cm T2: tumour >2 cm but <5 cm across. T3: tumour >5 cm across. T4a: tumour has spread into the chest wall T4b: tumour has spread into the skin and the breast might be swollen T4c: tumour has spread to both the skin and the chest wall T4d: inflammatory carcinoma

Assess the clinicopathological characteristics of cancer in the patients enrolled in the study. For this, it is used the Tumor, Node, Metastasis (TNM) staging system is the most common way that doctors stage breast cancer. Patient scans and tests give some information about the stage of the cancer.

Lymph Node (N) conditions describes whether the cancer has spread to the Lymph Nodes (LN). Prognosis is better when cancer has not spread to the LN. The more LN that contain cancer, the poorer prognosis tends to be.

Node cannot be assessed (NX): LN can't be assessed N0: no Cancer Cells (CC) N1: CC in the LN in the armpit but the nodes are not stuck to surrounding tissues.

N2a: CC in the LN in the armpit, which are stuck to each other and to other structures.

N2b: CC in the LN behind the breast bone. N3a: CC in LN below the collarbone. N3b: CC in LN in the armpit and behind the breastbone. N3c: CC in LN above the collarbone.

Assess the clinicopathological characteristics of cancer in the patients enrolled in the study. For this, it is used the Tumor, Node, Metastasis (TNM) staging system is the most common way that doctors stage breast cancer. Patient scans and tests give some information about the stage of the cancer.

Metastasis (M) describes whether the cancer has spread to a different part of the body.

M0 means that there is no sign that the cancer has spread. cMo(i+) means there is no sign of the cancer on physical examination, scans or x-rays. But cancer cells are present in blood, bone marrow, or lymph nodes far away from the breast cancer - the cells are found by laboratory tests M1 means the cancer has spread to another part of the body.

Cancer cells are given a Grade (G) when they are removed from the breast and checked under a microscope. The G is based on how much the cancer cells look like normal cells.

G1 or well differentiated (score 3, 4, or 5): cells are slower-growing, and look more like normal breast tissue.

G2 or moderately differentiated (score 6, 7): cells are growing at a speed of and look like cells somewhere between G1 and 3.

G3 or poorly differentiated (score 8, 9): cells look very different from normal and will probably grow and spread faster.

The histopathological differentiation is analyzed on tumor samples. The collection of a sample of the primary archival tumor and/or a sample of metastatic lesions will be requested, when available.

Receptors (R) are proteins in or on cells that can attach to certain substances in the blood. Normal breast cells and some breast cancer cells have R that attach to the hormones estrogen and progesterone, and depend on these hormones to grow.

Breast cancer cells may have one, both, or none of these R:

• Estrogen Receptors (ER) -positive: are called ER-positive (or ER+) cancers.
• Progesterone Receptors (PR) -positive: are called PR-positive (or PR+) cancers.
• Hormone receptor (HR) -positive: If the cancer cell has one or both of the R above, the term hormone-receptive positive (also called hormone-positive or HR+) breast cancer may be used.
• HR-negative: If the cancer cell has neither the ER nor the PR, it's called hormone-receptor negative (also called hormone-negative or HR-).

The hormonal R status is analyzed on tumor samples. The collection of a sample of the primary archival tumor and/or a sample of metastatic lesions will be requested, when available.

HER2 is a growth-promoting protein on the outside of all breast cells. Cells with higher than normal levels of HER2 are called HER2+. These cancers tend to grow and spread faster than other breast cancers, but are much more likely to respond to treatment with drugs that target the HER2 protein.

A biopsy or surgery sample of the cancer is tested with either immunohistochemical stains (IHC) or Fluorescent in situ hybridization (FISH).

• IHC result 0 or 1+: cancer is considered HER2-negative. These cancers do not respond to treatment with drugs that target HER2.
• IHC result is 3+: the cancer is HER2-positive. These cancers are usually treated with drugs that target HER2.
• IHC result is 2+: HER2 status of the tumor is not clear and is called "equivocal." HER2 status needs to be tested with FISH to clarify the result.

HER2 is analyzed on tumor samples. The collection of a sample of the primary archival tumor and/or a sample of metastatic lesions will be requested, when available.

Ki-67 is a protein in cells that increases as they prepare to divide into new cells. A staining process can measure the percentage of tumor cells that are positive for Ki-67. The more positive cells there are, the more quickly they are dividing and forming new cells. In breast cancer, a result of less than 10% is considered low, 10-20% borderline, and high if more than 20%.

Ki-67 is analyzed on tumor samples. The collection of a sample of the primary archival tumor and/or a sample of metastatic lesions will be requested, when available.

BRCA1 and BRCA2 are human genes that produce tumor suppressor proteins. These proteins help repair damaged DNA and, therefore, play a role in ensuring the stability of each cell's genetic material. When either of these genes is mutated, or altered, such that its protein product is not made or does not function correctly, DNA damage may not be repaired properly. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.

People who have inherited mutations in BRCA1 and BRCA2 tend to develop breast and ovarian cancers at younger ages than people who do not have these mutations.

BRCA1 and 2 mutations are analyzed on whole blood samples, that are preferably collected at the enrolment visit (after signing the informed consent).

Disease-free survival (DFS): It is defined as the time from date of initial breast cancer surgery to the date of the first documented relapse event (local, regional and/or distant) of the disease, second breast or non-breast primary tumor, or death due to any cause, whichever occurs first. In the event that none of the previous events were observed, censoring the last contact date will be considered.

Event-free survival (EFS): It is defined as the time from date of breast cancer diagnosis to the date of the first documented event of disease progression which excludes the potentially curative surgery, relapse (local, regional and/or distant) of the disease after the curative surgery, second breast or non-breast primary tumor, or death due to any cause, whichever occurs first. In the event that none of the previous events were observed, censoring the last contact date will be considered.

Progression-free survival (PFS): It is defined as the time from the start date of a specific treatment to the documentation of disease progression on such treatment, or death due to any cause, whichever occurs first. In the event that none of the previous events were observed, censoring the last contact date will be considered.

Overall survival (OS): It is defined as the time from date of initial breast cancer diagnosis to the date of death due to any cause.

Number of patients with breast cancer managed to get pregnant, spontaneously or through in vitro fertilization (IVF) methods, considering both the patients with early disease and the patients with advanced disease.

Regarding the live-born children, serious diseases and age until the progression is known.